MINI-REVIEW
Enzymatic synthesis of bioactive compounds with high potentialfor cosmeceutical application
Io Antonopoulou1& Simona Varriale2 & Evangelos Topakas3 & Ulrika Rova1 &
Paul Christakopoulos1 & Vincenza Faraco2
Received: 19 April 2016 /Revised: 22 May 2016 /Accepted: 24 May 2016# The Author(s) 2016. This article is published with open access at Springerlink.com
Abstract Cosmeceuticals are cosmetic products containing bi-ologically active ingredients purporting to offer a pharmaceuti-cal therapeutic benefit. The active ingredients can be extractedand purified from natural sources (botanicals, herbal extracts, oranimals) but can also be obtained biotechnologically by fer-mentation and cell cultures or by enzymatic synthesis and mod-ification of natural compounds. A cosmeceutical ingredientshould possess an attractive property such as anti-oxidant, an-ti-inflammatory, skin whitening, anti-aging, anti-wrinkling, orphotoprotective activity, among others. During the past years,there has been an increased interest on the enzymatic synthesisof bioactive esters and glycosides based on (trans)esterification,(trans)glycosylation, or oxidation reactions. Natural bioactivecompounds with exceptional theurapeutic properties and lowtoxicity may offer a new insight into the design and develop-ment of potent and beneficial cosmetics. This review gives anoverview of the enzymatic modifications which are performedcurrently for the synthesis of products with attractive propertiesfor the cosmeceutical industry.
Keywords Lipases . Feruloyl esterases . Tannases .
Transferases . Glycosidases . Proteases . Laccases .
Anti-oxidant . Anti-microbial . Anti-inflammatory . Skin
whitening . Anti-wrinkling . Anti-aging . Photoprotective .
Fungal . Bacterial
Introduction
Articles defined as cosmetics are intended for human bodyapplication aiming at increased beauty and attraction orcleaning use, without affecting the body structure or function(Nelson and Rumsfield 1988). During the last few years, thecosmetic industry is searching for bioactive compounds thatalso promote health benefits. This combination resulted in anew term called Bcosmeceutical^ where cosmetic productsassert medical benefits (Choi and Berson 2006).Cosmeceuticals are different from cosmetics and drugs, asthey affect the function and structure of skin, while havingdrug-like effects that are marketed using skin appearance-based claims. Cosmeceutical industry numbers over 400 man-ufacturers worldwide including Estée Lauder, L’Oréal, Procter& Gamble, and Avon, with 80 % of the US and Europeanmarket dedicated to skin care (Brandt et al. 2011). In 2008,Japan was by far the biggest market in cosmeceuticals valuedat $6–8 billion, followed by the USA ($5–6 billion) and EU($3–5 billion) (Kim and Wijesekara 2012). Market growth isexpected to rise in economies like China, Brazil, the RussianFederation, and India (Brandt et al. 2011). Nevertheless, theFood and Drug Administration (FDA) does not recognizecosmeceutical as a term even if it is widely used in industry,while in the EU, most are considered as cosmetics (Sharma2011). There is no regulation of cosmeceuticals in EU, theUSA, and Japan; however, as the interaction betweencosmetic and skin is complex, there is an increased attentiontowards the need of toxicological tests of the final product andits bioactive ingredients (Nohynek et al. 2010). Targetingredients of cosmeceuticals may include phytochemicals,
* Vincenza [email protected]
1 Division of Chemical Engineering, Department of Civil,Environmental and Natural Resources Engineering, Luleå Universityof Technology, 97187 Luleå, Sweden
2 Department of Chemical Sciences, University of Naples BFedericoII^, Naples, Italy
3 Biotechnology Laboratory, School of Chemical Engineering,National Technical University of Athens, 15700 Athens, Greece
Appl Microbiol BiotechnolDOI 10.1007/s00253-016-7647-9
vitamins, peptides, enzymes, essential oils among others, whichare incorporated into lotions, creams, and ointments dedicated toskin treatment. Desired properties, such as anti-oxidant, anti-aging, anti-microbial, anti-wrinkling, photoprotective, or skinwhitening, are preferentially offered by natural compoundsderived from plant or sea organisms, instead of chemicallysynthetic compounds. The guidelines of the Council of Europedefine a natural cosmetic as a product that consists of naturalsubstances of botanical, mineral, or animal origin, exclusivelyobtained through physical, microbiological, or enzymaticmethods, with certain exceptions for fragrances andpreservatives. This demand has increased the sales of personalcare products based on natural ingredients; however, often amodification of the bioactive compounds is required prior to
their application in the final product, e.g., by increasing itslipophilicity or improving its biological properties.Modification with fatty compounds generally results in morelipophilic products, whereas modification with sugars resultsin more hydrophilic derivatives. Chemical approaches havenumerous disadvantages such as the protection and de-protection of groups resulting in many reaction steps, use ofstrong acid as catalyst, high temperatures (150–200 °C), forma-tion of unwanted products, dark color, burnt taste of product,and high energy consumption (Kiran and Divakar 2001).Enzymatic modification is employed under mild conditions, ishighly selective, and includes one single step.
In this review, the most important enzymatic modificationsthat result to the synthesis of ingredients with attractive
Fig. 1 Reaction examples
Appl Microbiol Biotechnol
properties for the cosmeceutical industry are documented.Properties such as anti-oxidant, anti-inflammatory, anti-micro-bial, skin-whitening, and photoprotective effects were criteriafor the selection of the reported modification reactions. Amodification may follow different mechanisms: direct esteri-fication or transesterification performed by esterases (such aslipases, feruloyl esterases, or tannases) and proteases, glyco-sylation (reverse hydrolysis) or transglycosylation performedby transferases, and β-glucosidases and oligomerization per-formed by laccases. Examples of such modification reactionsare presented in Fig. 1.
Esterases
Except for their hydrolytic ability, esterases are able toperform (trans)esterification reactions. Triaglycerol li-pases (EC 3.1.1.3) are most commonly used due to theirbroad specificity, as shown in Table 1. Less popular,ferulic acid esterases (FAEs; EC 3.1.1.73) generally cata-lyze the hydrolysis of the ester bond between the mainchain polysaccharides of xylans or pectins and the mono-meric or dimeric ferulic acid in plants; however, they areable to modify hydroxycinnamic acids and their esters.Tannases (tannin acyl hydrolases, EC 3.1.1.20) are knownto be active on complex polyphenolics, catalyzing thehydrolysis or synthesis of the Bester bond^ (galloyl esterof an alcohol moiety) or the Bdepside^ bond (galloyl esterof gallic acid) (Battestin et al. 2008). Low water content isessential for the thermodynamic shift of equilibrium to-wards synthesis. Different systems have been employedincluding organic co-solvents, ionic liquids, solvent-freesystems, supercritical fluids, and molecular sieves as wa-ter removal agents. The ideal solvent should aid solubili-zation of substrates, not affect enzyme activity, have lowtoxicity, and enable easy product recovery (Wei et al.2002). Ionic liquids are a good alternative since they gen-erally do not deactivate esterases and have exceptionaltailorability and low volatility (Zeuner et al. 2011).However, a number of issues including the cost involvedin large-scale usage are to be addressed. Aids as micro-wave irradiation and ultrasound treatment have beenemployed in lipase-catalyzed reactions (Costa et al.2014; Cui et al. 2013). Detergentless microemulsions, sofar employed in FAE-catalyzed reactions, consist of a hy-drocarbon, a shor t -cha ined a lcohol , and waterrepresenting thermodynamically stable dispersions ofaqueous microdroplets in the hydrocarbon solvent(Khmelnitsky et al. 1988). An important advantage ofthese mixtures is the separation of reaction products andenzyme reuse, while the solubility of relatively polar phe-nolic acids is high owing to the presence of large amountof polar alcohol.
α-Hydroxy acid derivatives
α-Hydroxy acids (AHAs) are composed of carbon backbonescontaining a carboxyl group and a hydroxyl group on theadjacent carbon. Among them, glycolic acid, lactic acid, andmalic acid have been well known in cosmetics as beauty aidsand peeling agents due to their hygroscopic, emulsifying, andexfoliating properties (Tung et al. 2000). Short-chain AHAs aslactic acid are more active in regulating the rate of skin regen-eration and improving dryness (Wei et al. 2002). However,limiting factors for application are their acidicity and the rapidpenetration into the deep epiderm, causing irritant effects atconcentrations >10 %. To control their concentration and pen-etration to the skin’s intercellular spaces, AHAs have beengrafted onto alkylglycosides, fatty acids, or fatty alcohols sothey can be gradually released by the epidermis esterases.Short-chain alkylglycosides have been reported to relieve theirritant effects on skin after UV radiation (Wei et al. 2003). Amajor concern regarding enzymatic modification is that lacticacid can undergo self-polymerization at high temperatures andlow water content forming linear polyesters or lactones be-cause of the presence of groups that act as acyl donor andnucleophile at the same time (Roenne et al. 2005). A keyfactor is the choice of enzyme that favors the desired reaction.Lactic acid does not act as nucleophile when the lipase B fromCandida antarctica (CALB) is used as biocatalyst due to ste-ric hindrance at the enzyme’s active site (Form et al. 1997).Another obstacle is the severe inactivation of enzymes in highconcentrations of lactic acid or in solvent-free systems, as itdecreases the logP of the reaction medium (Pirozzi and Greco2004). Polar solvents aid lactic acid solubilization at higherconcentrations and seem to prevent enzyme inactivation be-cause they show an acid-suppressive effect due to their basic-ity (Hasegawa et al. 2008). However, esterification of glycolicacid has been favored in apolar hexane producing high yieldof glycolate ester (91 % after 24 h) (Torres and Otero 1999).Limitation of lactic acid self-polymerization has beenachieved in hexane although the esterification with fatty acidsresulted in lower yields (35 %) (Torres and Otero 2001).Transesterification between α-butyl glycoside and butyl lac-tate in a solvent-free system eliminating the butanol co-product under reduced pressure resulted in more than 95 %conversion and very high concentration of a less irritant prod-uct (170 g/L) in a single batch reaction (Bousquet et al. 1999).
Kojic acid derivatives
Kojic acid (5-hydroxy-2-(hydroxymethyl)-4H-pyran-4-one)is an inexpensive water-soluble fungal secondary metaboliteproduced by Aspergillus and Penicillium species. It possessesvaluable biological properties such as anti-oxidant, anti-mi-crobial, and anti-inflammatory, while as an iron and copperchelator has the capacity to prevent photodamage,
Appl Microbiol Biotechnol
Tab
le1
Lipase-catalyzedreactio
ns
Product
Donor
Acceptor
Enzym
eSolvent
system
Yield
(tim
e)T (°C)
Reference
Examples
ofα-hydroxy
acid
derivatives
C6–C18
lactates
C6–C18
fatty
alcohols
Lactic
acid
Novozym
435
Acetonitrile
94–96%
(48h)
30To
rres
andOtero
1999
C6–C18
glycolates
C6–C18
fatty
alcohols
Glycolic
acid
Novozym
435
Hexane
91%
(48h)
Ethyl
glycosidelactate
Ethyl
glycoside
Butyl
lactate
Novozym
435
Solvent-free
95%
(36h)
60Weietal.2002
β-M
ethylg
lycoside
malate/glycolate/lactate
β-M
ethylg
lycoside
Malic/glycolic/
lacticacid
Novozym
435
t-Butanol
48–75%
(120
h)60
Park
etal.2001
Palm
itoyl
orstearoyl
lactic
acid
C16
orC18:0
fatty
acid
Lactic
acid
Lipozym
eIM
20Ethyl
methyl
ketone
37.5–40%
(72h)
37or
60
Kiran
andDivakar2001
Examples
ofkojic
acid
derivativ
esKojicacidmonoricinoleate
Ricinoleicacid
Kojicacid
Lipozym
eTLIM
Solvent-free
87.4%
(6h)
80El-Boulifietal.2014
Kojicacid
monooleate
Oleicacid
Kojicacid
AmanoG
Acetonitrile
36.7%
(48h)
50Liu
andSh
aw1998
Kojicacid
monopalmitate
Palm
iticacid
Kojicacid
RM
IMAcetonitrile
29.30%
(12h)
50Lajisetal.2013
Examples
oflip
oicacid
derivativ
esPy
ridoxine-O
-lipoate(5′
and4′)/tyrosol-8-O-
lipoate/ty
ramin-8-N
-lip
oate
Pyridoxine
(vitamin
B6)
Lipoicacid
CNTs-C6-NH2-
CaL
Bor
CNTs-
C11-CH3-CaL
B
(mtoa)NTf2
91.1–99.5%
(72h)
60Papadopoulou
etal.2
013
Tyrosol/tyram
ine
(bmim
)PF6
Phenoliclipoates
4-Hydroxybenzyl
alcohol/vanillyl
alcohol/4-
hydroxyphenylethanol/coniferyl
alcohol/
dihydroxybenzylalcohol/dihydroxyphenyl
etha-
nol
Lipoicacid
Novozym
435
2-Butanone:
hexane
64–80%
(15h)
25Kakietal.2012
Octanyl
lipoate
n-Octanol
α-Lipoicacid
Whole-celllipase
from
Aspergillus
oryzae
WZ007
Heptane
75.2%
(48h)
50Yangetal.2009
Examples
ofarbutin
derivatives
Arbutin
lipoate
α-Lipoicacid
β-A
rbutin
Type
Blipasefrom
C.antarctica
t-Butanol
–(7
days)
55Ishiharaetal.2010
C2–C18
alkylarbutin
esters
Vinyl
estersof
C2–C18
aliphatic
alcohols
β-A
rbutin
Immobilizedlip
ase
from
Penicillium
expansum
Anhydrous
THF
82–99%
(0.5–72h)
35Yangetal.2010a
Arbutin
phenolicacid
esters
Vinyl
estersof
arom
aticacids
30–99%
(4–96h)
50Yangetal.2010b
Arbutin
fatty
acid
esters
Saturatedfatty
acids(C6–C18)
β-A
rbutin
ChirazymeL-2
C2
Acetonitrile
Upto
45%
(2days)
60Nagaietal.2009
Arbutin
ferulate
Ferulic
acid
β-A
rbutin
Type
Blipasefrom
C.antarctica
t-Butanol
57%
(7days)
55Ishihara
etal.2
010
Vinyl
ferulate
p-Arbutin
Novozym
435
Acetonitrile
50%
(−)
45Chigorimbo-M
urefuetal.
2009
Examples
ofvitamin
derivatives
L-A
scorbylp
almitate
Palm
iticacid
L-A
scorbicacid
Lipasefrom
Bacillus
stearothermophil-
usSB
1
Hexane
97%
(6h)
50Bradooetal.1999
Methylp
almitate
Lipasefrom
Burkholderia
multivoras
Solvent-free
(under
microwave
irradiation)
83%
(40min)
80Kidwaietal.2009
Ethyl
palm
itate
Lipozym
eTLIM
t-Butanol
20%
(120
h)40
Reyes-D
uarteetal.2011
Appl Microbiol Biotechnol
Tab
le1
(contin
ued)
Product
Donor
Acceptor
Enzym
eSolvent
system
Yield
(tim
e)T (°C)
Reference
Vinyl
palm
itate
100%
(120
h)Tripalm
itin
50%
(140
h)L-A
scorbylo
leate
Oleicacid
L-A
scorbicacid
Novozym
435
t-Amyl
alcohol
82%
(52h)
65Viklund
etal.2003
Methylo
leate
Lipozym
eTLIM
t-Butanol
50%
(−)
60Reyes-D
uarteetal.2011
Triolein
Novozym
435
t-Amyl
alcohol
84%
(140
h)40
Moreno-Perezetal.2013
Oliveoil
Novozym
e435-PE
I85
%(48h)
45Conjugatedlin
oleoyl
ascorbates
C9t11CLA
L-A
scorbicacid
ChirazymeL-2
C3
Acetone
~80%
(~48
h)50
Watanabeetal.2008
L-A
scorbylb
enzoate
Benzoicacid
L-A
scorbicacid
Novozym
435
Cyclohexanone
47.7%
(48)
66.6
Lvetal.2008
L-A
scorbylacetate
Vinyl
acetate
L-A
scorbicacid
Lipozym
eTLIM
Acetone
99%
(4)
40Zhang
etal.2012
Vitamin
Esuccinate
Succinicanydride
Rac-all-α-
tocopherol
Succinyl-N
ovozym
435
DMSO
:t-butanol
94.4%
(48h)
40Yin
etal.2011
Vitamin
Eacetate
Vinyl
acetate
δ-To
copherol
Novozym
435
t-Amyl
alcohol
65%
(16days)
60To
rres
etal.2008b
α-Tocopherol
>45
%(16days)
Vitamin
Eferulate
Ethyl
ferulate
Vitamin
ENovozym
435
Solvent-free
25.2%
(72h)
60Xin
etal.2011
Sugaror
ascorbyl
retin
yladipates
Sorbitol/fructose/glucose/
saccharose/m
altose/ascorbicacid
Retinyl
adipate
Novozym
435
t-Amyl
alcohol
22–80%
(45h)
40Rejasse
etal.2003
Vitamin
Alactate
Lactic
acid
Vitamin
Aacetate
Immobilizedlipase
from
C.
antarctica
Hexane
32%
(7h)
30Liu
etal.2012
Methyllactate
Retinol
Lipozym
e86
%(50h)
55Maugard
andLegoy
2000
Vitamin
Aoleate
Methylo
leate
Hexane
90%
(50h)
Oleicacid
Retinyl
acetate
Immobilizedlipase
from
C.
antarctica
79%
(7h)
30Liu
etal.2012
Vitamin
Asaturatedfatty
acid
esters(C6–C18)
C6–C18
saturatedfatty
acids
Hexane
51–82%
(7h)
Vitamin
Amethyl
succinate
Dim
ethylsuccinate
Retinol
Lipozym
eHexane
77%
(50h)
55Maugard
andLegoy
2000
Examples
offlavonoidderivativ
esQuercetin
derivatives
C18–C
12fatty
acids
Isoquercetin
Novozym
435
Acetone
oracetonitrile
81–98%
(18–24
h)45–
60
Ziaullah2013
Ethyl
estersof
C4–C18
fatty
acids
Novozym
435
t-Amyl
alcohol
38–66%
(72h)
65Salem
etal.2010
Cinnamicacids
Novozym
435
t-Butanol
17–89%
(7days)
60Stevensonetal.2006
Dibenzylm
alonate
Lipasefrom
C.antarctica
Me 2CO:p
yridine
74%
(12days)
45Riva1996
Vinyl
acetate
PSL-C
IIAcetone
84%
(96h)
50Ch-
ebiletal.2007
Quercetin
100%
(24h)
Silybinderivativ
esDivinyl
esterof
decanoicacid
Silybin
Novozym
435
Acetonitrile
26–66%
(72h)
45Vavrikova
etal.2014
Vinyl
butanoate
Novozym
435
Acetone
100%
(24–96
h)50
Theodosiouetal.2009
Vinyl
acetate
Novozym
435
Acetone
92%
(48h)
35Gazak
etal.2010
Esculin
derivativ
esFatty
acids,dicarboxylicacids,othercyclicacids
Esculin
Novozym
435
t-Amyl
alcohol
13–90%
(12h)
60Ardhaouietal.2004a
Palm
iticacid
Novozym
435
TOMATF2
N>96
%(6
days)
60Lue
etal.2010
Vinyl
butyrate
Novozym
435
[Bmim
]BF6
90.6%
(72h)
60Katsouraetal.2007
Phloridzin
derivativ
esC2–C18
fatty
acids
Phloridzin
Novozym
435
Acetonitrile
70–90%
(7days)
65Milisavljecicetal.2014
Appl Microbiol Biotechnol
Tab
le1
(contin
ued)
Product
Donor
Acceptor
Enzym
eSolvent
system
Yield
(tim
e)T (°C)
Reference
Ethyl
cinnam
ate
Novozym
435
Solvent-free
100%
(4h)
80Enaud
etal.2004
Hesperedinderivativ
esDecanoicacid
Hesperidin
Novozym
435
[Bmim
]BF4
:acetone
53.6%
(96h)
50Brancode
Araujoetal.
2011
Palm
iticacid
Novozym
SP435
t-Amyl
alcohol
Upto
40%
(12h)
60Ardhaouietal.2004b
Vinyl
acetate
Hesperetin
PSL-C
IIAcetonitrile
30%
(96h)
50Chebiletal.2007
Rutin
derivativ
esC4–C18
fatty
acids
Rutin
CALB
t-Amyl
alcohol
27–62%
(168
h)60
Viskupicova
etal.2010
Ethyl
linoleate
Novozym
435
Acetone
50%
(96h)
50Mellouetal.2
006
Methylp
almitate
Novozym
435
t-Amyl
alcohol
30%
(48h)
60Passicos
etal.2004
Vinyl
estersof
fatty
acids
Novozym
435
[Bmim
]BF4
15–65%
(96h)
60Katsouraetal.2006
Dicarboxylic
acids,fatty
acids,
othercyclicacids
Novozym
435
t-Amyl
alcohol
10–90%
(−)
60Ardhaouietal.2004a
Divinyl
dicarboxylate
Novozym
435
t-Butanol
36%
(4days)
50Xiaoetal.2005
Dibenzylm
alonate
Lipasefrom
C.antarctica
Me2CO:pyridine
79%
(12h)
45Riva1996
Vinyl
cinnam
ate
ChirazymeL-2
Acetone
28%
(14h)
37Ishihara
etal.2002
Naringinderivativ
esα-Linolenicacid,linoleic,oleicacid
Naringin
Novozym
435
t-Amyl
alcohol
83.2–90.1%
(72h)
(assisted
byultrasound
irradiation)
50Zheng
etal.2013
Stearicacid
Novozym
435
t-Amyl
alcohol
46%
(24h)
60Duanetal.2006
Vinyl
butyrate
Novozym
435
[Bmim
]BF 4
86.9%
(100
h)60
Katsouraetal.2007
Methylp
almitate
Novozym
435
t-Amyl
alcohol
92%
(48h)
60Passicos
etal.2004
C10–C
12vinylestersof
saturatedfatty
acids
Novozym
435
Acetone
22–70%
(96h)
50Mellouetal.2005
PUFA
from
byfish
products
Novozym
435
t-Amyl
alcohol
30%
(96h)
50Mbatia
etal.2011
Vinyl
laurate
Lipozym
eIM
TL
t-Amyl
alcohol
90%
(30min)
52Luo
etal.2013
Lauricacid
ChirazymeL-2
C2
Acetonitrile
~45%
(~30
h)60
Watanabeetal.2009
Ricinoleicacid
Immobilizedlipase
from
C.
antarctica
Acetone
24%
(120
h)50
Alm
eida
etal.2012
Castoroil
33%
(120
h)
Vinyl
cinnam
ate
ChirazymeL-2
Acetone
64%
(14days)
37Ishihara
etal.2002
Dibenzylm
alonate
Lipasefrom
C.antarctica
Acetone:
pyridine
69%
(12days)
45Riva1996
Vinyl
acetate
Naringenin
PSL-C
IIAcetonitrile
100%
(96h)
50Chebiletal.2007
Examples
ofhydroxycinnamicacid
derivatives
Feruloylated
lipids
Ferulic
acid
Glycerol
ChirazymeL2C-2
Solvent-free
80%
(>3h)
80Matsuoetal.2008
Trilin
olenin
Novozym
435
Hexane:2-
butanone
14%
(5days)
55Sabally
etal.2006
Flaxseed
oil
Novozym
435
SCCO2medium
57.6%
(27.5h)
80Ciftciand
Saldana2012
Ethyl
ferulate
Oleyl
alcohol
Novozym
435
Hexane
99.17%
(4days)
60Chenetal.2
011b
Triolein
Novozym
435
Toluene
77%
(144
h)60
Com
pton
etal.2000
Oliv
eoil
Novozym
435
2M2B
:toluene
59.6%
(2.34h)
60Radzietal.2014
Tributyrin
Novozym
435
Solvent-free
94.2%
(120
h)50
Zheng
etal.2008
Monostearin
Novozym
435
Ethanol
97.8%
(23h)
74Su
netal.2013a,b
Soybeanoil
Novozym
435
Glycerol
70%
(140
h)60
LaszloandCom
pton
2006
Fish
oil
Novozym
435
Toluene
80.4%
(5days)
70Yangetal.2
012
Phosphatidylcholine
Novozym
435
Chloroform
40.51%
(4days)
55Yangetal.2
013
Glycerol
Novozym
435
EMIM
TF2
N100%
(12h)
70Su
netal.2013a,b
Oleicacid
Novozym
435
Solvent-free
96%
(1.33h)
60Su
netal.2007
Appl Microbiol Biotechnol
Tab
le1
(contin
ued)
Product
Donor
Acceptor
Enzym
eSolvent
system
Yield
(tim
e)T (°C)
Reference
Glycerylferulate
Oleicacid
Novozym
435
[Bmim
]PF6
100%
(3h)
80Su
netal.2009
Vinyl
ferulate
Triolein
Novozym
435
Solvent-free
91.9%
(62h)
55Yuetal.2010
Methylcaffeate
Caffeicacid
Methanol
Novozym
435
[Bmim
][Tf 2N]
99.79%
(9h)
75Wangetal.2015
Propyl
caffeate
Methylcaffeate
1-Propanol
Novozym
435
[Bmim
][CF3SO
3]
99.5%
(2.5h)
60Wangetal.2013
Sitosteryl
hydroxycinnamates
Vinyl
ferulate/caffeate/sinapate
Sitosterol
Lipasetype
VIIfrom
Candida
rugosa
Hexane:2-
butanone
30–90%
(−)
45TanandSh
ahidi2011;Tan
andSh
ahidi2
012;
Tan
andSh
ahidi2
013
Examples
ofgallo
ylderivatives
Propyl
gallate
Gallic
acid
1-Propanol
Immobilizedlipase
from
Staphylococcus
xylosus
Hexane
90%
(6h)
52Bouazizetal.2010
Mono-,di-,and
tri-acety-
latedEGCG
Vinyl
acetate
EGCG
Lipozym
eRM
IMAcetonitrile
87.37%
(1.13h)
40Zhu
etal.2014
Catechin5-Oand7-O
acetate
Vinyl
acetate
Catechin
PCL
Acetonitrile
70%
(48h)
45Lam
bustaetal.1993
Novozym
435:
lipaseBfrom
Candida
antarcticaim
mobilizedon
amacroporous
acrylic
resin(CALB);lip
ozym
eIM
20/lipozymeRM
IM:lipasefrom
Rhizomucor
mieheiimmobilizedon
duolite
anion
exchange
resion;lipozym
eTLIM
:lipasefrom
Thermom
yces
laniginosusim
mobilizedon
silicagranulation;am
anoG:lipasefrom
Penicillum
camem
berti;CNTs-C
6-N
H2-CaL
B,C
NTs-C
11-CH3-CAL-B:
novozym
435functio
nalized
with
variousmulti-walledcarbon
nanotube
groups;chirazymeL-2:immobilizedlip
aseBfrom
C.A
ntarctica;
succinyl-novozym
435:
novozym
435modifiedwith
succinic
anhydride;PS
L-C
II,P
CL:lipasefrom
Pseudom
onas
cepacia
Appl Microbiol Biotechnol
hyperpigmentation, and skin wrinkling. Its primary use incosmetics is as a skin whitening agent but there are concernsregarding its skin compatibility, oil solubility, and storage sta-bility even at ordinary temperatures. Additionally, there isevidence of toxicity, irritancy, and carcinogenicity (Lajiset al. 2012). The first attempts on the enzymatic modificationof kojic acid focused on the synthesis of kojic acid glycosidesusing a sucrose phosphorylase from Leuconostocmesenteroides, an α-amylase from Bacillus subtilis and animmobilized β-galactosidase from Bacillus circulans(Nishimura et al. 1994; Kitao and Serine 1994; Hassan et al.1995). However, many lipophilic derivatives such as saturatedfatty (C6-C18) acid esters and the unsaturated kojic acidmonoricinolate and monooleate have been synthesized bycommercial lipases (Liu and Shaw 1998; Lajis et al. 2013;Khamaruddin et al. 2008; El-Boulifi et al. 2014; Ashari et al.2009). A phospholipase from Streptomyces sp. has synthe-sized phosphatidylkojic acid at 60 % yield from adipalmitoylphosphatidyl residue (Takami et al. 1994). Kojicacid has two OH– groups, the primary at C-7 and the second-ary one at C-5 which is essential to the radical scavenging andtyrosinase interference activity. Many derivatives have beensynthesized by modifying the 5-OH group; nevertheless,CALB showed moderate yield (53 %) synthesizing a laurateproduct esterified at the primary C-7 (Kobayashi et al. 2001;Chen et al. 2002).
Lipoic acid derivatives
α-Lipoic acid is a dithiol compound containing two sulfuratoms at the C-6 and C-8 carbons connected by a disulfidebond. It takes part in the anti-oxidant defense system of thecell through its ability to scavenge free radicals both in lipidand aqueous environments. This amphiphilicity constitutes itan ideal candidate for use in both oil- and water-based formu-lations. Moreover, it participates in the regeneration of anti-oxidants (i.e., vitamic C, vitamin E) and in the de novo syn-thesis of endogenous anti-oxidants (i.e., glutathione) andshows metal ion chelating activity, while it can repair oxida-tive damage in macromolecules (Papadopoulou et al. 2013).Other attractive properties include anti-inflammatory activity,aid in the treatment of diseases such as diabetes, atherosclero-sis, cardiovascular, heavy-metal poisoning, radiation damage,cancer, Alzheimer’s, and AIDS (Maczurek et al. 2008).Synthesis of lipoic acid phenolic derivatives by CALBshowed that a prior aromatic hydroxylation of the donor of-fered higher 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicalscavenging activity to the products. The hydroxytyrosol esterof lipoic acid showed similar anti-oxidant activity to α-tocopherol but higher than the commercial butylated hydroxy-toluene (BHT) (Kaki et al. 2012). Lipoic acid is found in aracemic mixture, where the (R)-enantiomer is much more ac-tive than the (S)-enantiomer. Only lipases from Candida
rugosa and Aspergillus oryzae (whole cell) have been reportedto enable kinetic resolution of racemicα-lipoic acid (Yan et al.2009; Fadnavis et al. 1998).
Hydroquinone derivatives
Hydroquinone, a phenolic compound with two –OH groups atthe para positions of the benzene ring, has been commerciallyused in cosmetics at concentrations <1 % as an anti-oxidant,fragrance, reducing agent, or polymerization inhibitor(Andersen et al. 2010). Its most promising use is as a skinwhitening agent; however, it is prone to cause irritations anddermatitis (Kang et al. 2009). Its glycosylated derivative,arbutin, has attracted attention as a better tyrosinase inhibitorwhen compared to conventional agents as it inhibits melano-genesis without causing melanocytotoxicity (Sugimoto et al.2005). It also plays an important role in scavenging free rad-icals, as an anti-inflammatory, and an anti-microbial agent(Lee and Kim 2012). Αrbutin has two isomers (α- and β-).The first is synthesized by chemical or enzymatic methods andshows higher efficiency and stability while the latter is extract-ed from natural sources such as bearberry, cranberry, blueber-ry, and pears (Seo et al. 2012a).α-Arbutin possesses a 10-foldstronger inhibitory effect on the activity of tyrosinase fromhuman malignant melanoma cells compared to its anomer,whereas β-arbutin reduces tyrosinase activities from mush-room and mouse melanoma (Seo et al. 2012b). α-Arbutinshows extremely increased browning resistance to light irra-diation compared to hydroquinone (Kitao and Sekine 1994).Lipases have been used for the acylation of β-arbutin witharomatic or fatty acids showing absolute regioselectivity atthe 6′ position. This phenomenon can be attributed to thehypothesis that the primary OH– group of the sugar moietyis less hindered so it can enter more easily into the active siteof the lipase and attach the acyl-enzyme intermediate. Studieson immobilized lipase from Penicillium expansum showedthat the elongation of the donor chain length (C2–C8) resultsin higher initial yields perhaps due to stronger interactionswith the hydrophobic acyl binding site of the enzyme.Branched-chain acyl donors affect negatively the initial ratedue to steric strain while the presence of a conjugated C–Cdouble bond adjacent to the carbonyl moiety decreases the ratesubstantially (Yang et al. 2010a). The radical scavenging ac-tivity of acyl (C6–C18) arbutin is independent of the chainlength (Nagai et al. 2009). Fatty acid derivatives of arbutinshow higher anti-melanogenesis and anti-oxidant activity thanarbutin which could be allied to the improved membrane pen-etration, due to increased lipophilicity (Watanabe et al. 2009).Synthesized by CALB, arbutin ferulate was found to have19 % higher activity against the 2,2′-azino-bis(3-ethylbenzo-thiazoline-6-sulphonic acid (ABTS) free radical than ferulicacid and be 10 % more efficient towards low-density lipopro-tein (LDL), showing higher anti-oxidant than Trolox, a well-
Appl Microbiol Biotechnol
known analog of vitamin E and commercial anti-oxidant(Chigorimbo-Murefu et al. 2009).
Vitamin derivatives
L-Ascorbic acid (vitamin C) is a potent water-soluble naturalanti-oxidant that has been used in cosmetics as a preservative,pH adjuster, or/and an active compound. It has been provedthat ascorbates promote collagen synthesis in human skin fi-broblasts in vitro up to eightfold capacity, while they showphotoprotective activity against UVA and UVB irradiationand have wound healing properties (Murad et al. 1981).Drawbacks as instability, poor liposolubility, and low skinpenetrability have led to modifications. Common saturatedfatty acid derivatives, as ascorbyl palmitate and ascorbyl stea-rate, have been synthesized showing that there is no negativeeffect on the radical scavenging activity by introducing a sat-urated group at the C-6 position of ascorbic acid (Watanabeet al. 2003). Enzymatic synthesis of ascorbyl palmitate is fo-cused on the esterification of palmitic acid with a vast use ofCALB in organic solvents or ionic liquids. Other commerciallipases have been employed offering varying yields (6–97 %)(Gulati et al. 1999; Costa et al. 2014; Park et al. 2003; Hsiehet al. 2006, Bradoo et al. 1999). However, saturated fatty acidesters still show moderate solubility in oils. Further improve-ment can be done by introducing a double bond in the fattyacid, resulting in superior products in terms of solubility andradical scavenging capacity. For instance, oleic acid is readilyavailable and inexpensive (Viklund et al. 2003). There arereports on esterification of olive oil, palm oil, or lard offeringa simple, direct, and natural route for synthesis (Moreno-Perezet al. 2013; Zhao et al. 2014; Burham et al. 2009).Derivatization of L-ascorbic acid requires mild conditions toprevent oxidation of both acid and its esters and high regiose-lectivity for the 6-O-position which is achieved by lipases(Zhang et al. 2012). However, the demand of polar solventsfor enhancing substrate solubility tends to be deleterious fortheir stability. Coating is an effective way to protectimmobilized lipases from denaturation reducing the interac-tions with the solvent (Moreno-Perez et al. 2013). The use ofvinyl ester donors increases the reaction rate, but implies therelease of fatty acids from oils and their further activation. Forinstance, CALB offered 100 % conversion of vinyl palmitatein t-butanol (Reyes-Duarte et al. 2011). When methyl estersare used, the by-product methanol is insoluble in oils, getsadsorbed onto the surface of the immobilized lipase, and leadsto negative effects on enzyme activity and operationalstability.
Vitamin E is a general term for a group of amphiphiliclipids, comprising of four tocopherols, having a saturatedphytyl side chain attached to the chromanol core and fourtocotrienols having an attached unsaturated isoprenoid sidechain. The analogs differ with each other by the presence
and placement of methyl groups around the aromatic ring. Innature, vitamin E occurs only in the RRR-form, while RRR-α-tocopherol is the most bioactive. Synthetic vitamin E (α-tocopherol) is a racemic mixture of eight stereoisomers inequal amounts (all-rac-α), of which not all are as bioactiveas the natural form (Torres et al. 2008a). Vitamin E is non-irritant to the eyes and skin, has high anti-oxidant activity withanti-aging and anti-tumor potential, inhibits the UVB-inducedlipid peroxidation, and shows skin-improving properties withanti-inflammatory and beneficial effect on the skin barrierfunction (Zondlo Fiume 2002). However, it is readilydestabilized by light and oxygen. Non-enantioselective acety-lation of vitamin E at the C-6 carbon has been performed onlyby CALB among other tested enzymes which can be ex-plained by studies that show that the acceptor binding site isdeeper in lipase B (Torres et al. 2008b; Pleiss et al. 1998). δ-Tocopherol gave higher rates due to its lower methylationdegree, while competitive acetylation experiments indicatedthat there is steric hindrance caused by the aliphatic chain andnot the chromanol ring. Vitamin E succinate has been synthe-sized by modified CALB yielding 94 % and by a lipase fromC. rugosa with moderate yields (Yin et al. 2011; Jiang et al.2013). Synthesized at lower yields (25.2 %) by CALB, novelvitamin E ferulate inhibits melanogenesis in humanmelanomacells, being an attractive candidate as a skin-whitening agent(Xin et al. 2011).
VitaminA includes a group of unsaturated compounds, i.e.,retinol, retinoic acid, and retinaldehyde, which are widelyused in cosmetic and skin care products because of their an-ti-oxidant, anti-aging, and skin-whitening properties. Retinolis the most active form of vitamin A; however, retinoids arereadily oxidized in air and inactivated by UV light while theyare water-insoluble and skin-irritating (Maugard and Legoy2000). The most common modification of retinol is retinylpalmitate, which is stable, slightly irritating, and not sensitiz-ing at concentrations between 0.1 and 1 % (CIR 1987). It hasbeen synthesized by the esterification of palmitic acid usingCALB, a lipase from Candida sp. and a modified lipase fromPseudomonas fluorescens (Ajima et al. 1986; Yin et al. 2006;Liu et al. 2012). Other vitamin A modifications include satu-rated fatty acid esters, oleate, lactate, and succinate/methylsuccinate derivatives catalyzed by CALB orRhizomucor miehei lipase (Maugard and Legoy 2000; Liuet al. 2012). Rejasse et al. (2003) proposed a vitamin Ainter-esterification reaction using CALB. The first step includ-ed esterification of adipic acid with retinol in t-amyl alcohol,while after 24 h, a polyol was added resulting in products withvarying yields (22–80 %).
Flavonoid derivatives
Aglycon and glycosylated flavonoids are natural compoundsof plant origin that have aroused interest for their anti-viral,
Appl Microbiol Biotechnol
anti-allergic, anti-inflammatory, anti-oxidant activities, andthe protection against cardiovascular diseases and cancer(Salas et al. 2011). Their basic structure is derived from 2-phenylbenzo-γ-pyran, where the original skeleton is substitut-ed with numerous OH– groups that result in a considerablyhydrophilic nature. The effect of acyl donors on esculin andrutin modification byCALB has been studied inmicroreactorsoffering conversion rates higher than 9.5 10−2 mmolL−1 h−1(Ardhaoui et al. 2004a). Naringin esterification in acontinuous flow microreactor offered more than 85 % conver-sion to 6-O″-monoesters. Regioselective acylation inmicroreactors offers mild reaction conditions, short reactiontimes, and high yields (Luo et al. 2013). Vinyl esters of satu-rated fatty acids are more reactive giving approximately athreefold increase in the conversion of naringin (Mellouet al. 2005). The enzymatic acylation of two isolatedchrysoeriol glucosides by CALB resulted in products withhigher anti-oxidant and anti-microbial activity against Gram-negative and Gram-positive bacteria that can be attributed tothe increased interaction of the hydrophobic chain with thecell membrane due to modified lipophilicity. Irilone, chrysin,and dihydromyricetin acetate have been synthesized byPseudomonas (syn Burkholderia) cepacia lipases and animmobilized lipase from P. expansum (Nazir et al. 2009;Chebil et al. 2007; Li et al. 2015). Orientin, vitexin, salicinfatty acid esters, and helicin butyrate have been synthesized byCALB (Liu et al. 2015; Katsoura et al. 2007). Silibyn, whichoccurs in nature as an equimolar mixture of two diastereoiso-mers (A and B) with different biological activities, has beenacylated by CALB at the C-23 position producing new anti-viral and anti-tumor compounds (Gazak et al. 2010).Modification (e.g., methylation) of the C-7 OH which bearsa pro-oxidant potential significantly improves the anti-radicalactivity of silybin.
The nature of flavonoid and the origin of lipase are crucialfor product formation. Generally, flavonoids with a primaryOH– group on the glycosyl moiety as naringin are more reac-tive than those with secondary OH– groups only, as rutin.Chebil et al. (2007) showed that isoquercetrin, the glycosylat-ed form of quercetin, could be acylated by both CALB andP. cepacia lipase (PSL) although only the latter could acylatequercetin. In the absence of the 4′-OH group of quercetin(hesperetin), PSL showed preference for the 7-OH group,followed by the 3′-OH group which can be explained by sterichindrance from the C-4′methoxy group. Chrysin was acylatedonly at the 7-OH group since the 5-OH group is not reactivewhen a 4-oxo group is present in the structure of the flavonoid.Molecular modeling regarding the regioselectivity of CALBshowed that the aglycon part of both rutin and isoquercitrinwas localized at the entrance of the enzyme’s binding pocketstabilized by hydrogen bond and hydrophobic interactions (deOliveira et al. 2009). The sugar part was placed close to thepocket bottom. Only the primary 6′-OH group of isoquercitrin
glucose and the secondary 4″-OH group of rutin rhamnosewere expected to be acetylated as they were the only ones tostabilize simultaneously near the catalytic histidine and theacetate bound to the catalytic serine. CALB synthesizedmonoesters on the primary OH of glucose moiety of esculinand on the secondary 4″′-OH of the rhamnose residue of rutin(Ardhaoui et al. 2004b). Acylation of quercetin was notachieved as the 4′-OH is conjugated with the C-4 carbonylgroup favoring a planar formation of the molecule, whichmay not be suitable for the catalytic site of the enzyme(Nazir et al. 2009).
Hydroxycinnamic acid derivatives
Hydroxycinnamic acids (HCAs; ferulic, FA; p-coumaric,p-CA; caffeic , CA; sinapic, SA) are a class ofphenylpropanoids known as more active anti-oxidantsthan hydroxybenzoic acids due to the presence of theC=COOH group (Widjaja et al. 2008). They are ubiqui-tous in nature as a component of arabinoxylans in plantcell walls offering linkage with lignin while they presentbroad spectrum of biological activities including anti-bac-terial, anti-viral, anti-inflammatory, anti-carcinogenic, an-ti-HIV, and anti-tumor effects (Tan and Shahidi 2012).However, their solubility is poor in hydrophilic and lipo-philic media. Among many natural photoprotectiveagents, feruloylated lipids have gained attention due totheir strong anti-oxidant, skin-whitening, anti-wrinkling,and UV absorptive ability (Radzi et al. 2014). FA is be-lieved to suppress melanin generation by antagonizingtyrosine because its structure is similar to tyrosine(Chandel et al. 2011). Enzymatic synthesis of green sun-screens offers stability and selectivity in contrast withchemical synthesis that is limited due to heat sensitivityand oxidation susceptibility of FA in alkaline media. Atwo-step synthesis of feruloylated diacylglycerols usingCALB has been proposed by Sun et al. (2007) includingthe transesterification of ethyl ferulate with glycerol andthe subsequent transesterification of glyceryl ferulate witholeic acid offering high yield of products (up to 96 %).Esterification of FA to glyceryl ferulate by CALB hasbeen performed in a continuous reactor reaching 80 %conversion and productivity of 430 kg/m3/reactor day(Matsuo et al. 2008). Biocatalysis under vacuum-rotaryevaporation contributes to increased conversion by elimi-nating external mass transfer resistance, effective interac-tion among different phases of enzymatic reaction, mini-mizing the negative effects of by-product ethanol (whenethyl ferulate is used as donor) on lipase activity (Xinet al. 2009). 1,3-Diferuloyl-sn-glycerol has been synthe-sized by CALB in a pilot plant scale bed reactor as by-product of the transesterification of ethyl ferulate withsoybean oil (Compton and Laszlo 2009). One hundred
Appl Microbiol Biotechnol
twenty kilograms of diferuloyl glycerol by-product couldbe isolated annually. Enzymatic esterification of olive,flaxseed, and fish oil offers low cost and greener config-urations to the process (Ciftci and Saldana 2012; Yanget al. 2012; Radzi et al. 2014). Transesterification of ethylferulate with castor oil, catalyzed by CALB, yielded62.6 % lipophilic and 37.3 % hydrophilic products (Sunet al. 2014). Esterification of FA with fatty (C2–C8) alco-hols improves the anti-oxidant capacity towards the oxi-dation of HDL, LDL, and total serum. Probably, the lipo-philic properties of anti-oxidants affect their incorporationinto the lipid part of lipoproteins reaching the site oflipoperoxidation, accounting for the increased anti-oxidant activity (Jakovetic et al. 2013).
Transesterification of methyl caffeate to propyl caffeate byCALB was performed in a continuous flow packed bedmicroreactor offering 99.5 % yield. The calculated kineticconstant Km was 16 times lower than than of a batch reactor(Wang et al. 2013). Caffeic acid phenethyl ester (CAPE) is aflavonoid-like compound and one of the major components ofhoneybee propolis possessing anti-inflammatory, anti-carci-nogenic, and neuroprotective properties (Widjaja et al.2008). High yield CAPE synthesis has been performed byCALB in a packed bed reactor, using ultrasound treatmentor in one-pot reactions using organic solvents or ionic liquids(Chen et al. 2010, 2011a; Ha et al. 2012; Wang et al. 2014).One-pot synthesis of a CAPE analog, 3-cyclohexyl caffeate,has been performed by esterification of caffeoylquinic acidsderived from coffee beans with methanol using a chlorogenatehydrolase followed by the transesterification of methylcaffeate with 3-cyclohecylpropyl caffeate using CALB in[Bmim][NTf2] (Kurata et al. 2011). Synthesized by a C.rugosa lipase, phytosteryl caffeate showed twofold increasein oxygen radical absorbance capacity (ORAC) comparing tothe parent vinyl HCA, while phytosteryl ferulate showed a 10-fold increased anti-oxidant activity compared to Trolox and atwofold increase comparing to vinyl ferulate (Tan and Shahidi2011, 2012). Chigorimbo-Murefu et al. (2009) synthesizedarbutin and hydroxyl steroid esters of FA in t-methyl-ethylether showing higher anti-oxidant activity than Trolox andtheir starting hydroxycinnamate. Arbutin ferulate possessed19 % higher anti-radical activity against ABTS free radicalthan FA and inhibited 10 % more efficiently LDL oxidationthan its precursors.
Although FAEs are less stable in organic media and lowwater content than lipases, they show higher substrate speci-ficity (Zeuner et al. 2011). Some examples of FAE-catalyzedreactions are presented in Table 2. In 2001, Giuliani et al.succeeded for the first time the synthesis of 1-pentyl-ferulateusing a FAE from Aspergillus niger in a water-in-oilmicroemulsions. Since then, novel FAEs from filamentousfungi such as Fusarium oxysporum, Myceliophthorathermophila (syn Sporotrichum thermophile), and
Talaromyces stipitatus have been employed in detergentlessmicroemulsions for the transesterification of methyl donors toalkyl hydroxycinnamates , fe ruloyla ted-arabino-oligosaccharides showing regioselectivity for the primary hy-droxyl group of the non-reducing arabinofuranose ring andother sugar ferulates (Topakas et al. 2003a; Vafiadi et al.2005, 2006, 2007b, 2008a). Although esterification with fattyalcohols generally results in more lipophilic products, theglyceryl esters of HCAs have been proved more hydrophilicthan their donors. Fed-batch esterification of FA withdiglycerin was performed by a FAE from A. niger under re-duced pressure yielding 69 % feruloyl and 21 % diferuloyldiglycerols (Kikugawa et al. 2012). The major product (FA-DG1) showed highest water solubility while all productsmaintained their radical scavenging activity against DPPHand their UV absorption properties. Diferuloyl diglycerolsshowed a twofold increase of anti-oxidant activity comparingto feruloyl diglycerols and FA. Esterification of SA and p-CAwith glycerol yielded 70 % glycerol sinapate and 60 % glyc-erol-p-coumarate, respectively, with indication of the forma-tion of minor dicinnamoyl glycerol esters (Tsuchiyama et al.2007). The ability of glycerol sinapate to scavenge DPHHradicals was higher than BHT while it maintained its UV ab-sorption properties.
Galloyl derivatives
Tannins, natural occurring polyphenols that can be found inpine and spruce bark, vegetables, and fruits, are categorizedinto hydrolysable, condensed, and complex. The simplest hy-drolysable tannins, commonly named gallotannins, consist ofgallic acid molecules esterified to a core polyol. The biocata-lytic synthesis of gallic acid esters is performed mainly bytannases and may follow different routes: (1) hydrolysis oftannic acid into gallic acid and further esterification to galloylesters, (2) direct esterification of tannic acid into a galloylester, or (3) transesterification of galloyl esters into anotherester. Examples of tannase-based reactions are presented inTable 3. A well-known synthetic galloyl ester widely used inskin cleaning/care products, make up, sunscreen, and tanningproducts is propyl gallate. Its biological activities are not lim-ited to the free-radical scavenging ability as it exhibits anti-microbial, anti-nociceptive activity, ultraviolet (UV) radiationprotection, anti-cariogenesis, anti-mutagenesis, and anti-carcinogenesis effects. However, in cosmetic formulations,its concentration is low (up to 0.1 %) due to indications forskin irritation or sensitization (CIR 2007). Applications ofpropyl gallate expand into the food, pharmaceutical, adhesive,lubricant, and biodiesel industry where it has been used as ananti-oxidant additive, for more than 20 years (Zhang 2015).
The majority of tannases used for the synthesis of propylgallate are carrier-bound or modified. A mycelium-boundtannase from A. niger esterified gallic acid at 65 % yield (Yu
Appl Microbiol Biotechnol
et al. 2007), whereas its microencapsulation by a chitosan-alginate complex showed more moderate results (Yu and Li2005). Mycelia could protect the enzyme from the harshnessof organic solvents as an immobilization matrix does and offeravoidance of costly and time-consuming purifications.Tannases from Aspergillus species, Lactobacillus plantarum,and Emericella nidulans immobilized on different carriers,catalyzed the esterification of tannic acid in organic and aque-ous media offering high yields (43–88%) (Fernandez-Lorenteet al. 2011; Prasad et al. 2011; Nie et al. 2012a; Goncalveset al. 2013). A bioimprinted commercial tannase esterified
tannic acid with propanol resulting in 50 % yield increasecompared to the non-imprinted enzyme. Bioimprinting locksthe enzyme into a favorable conformation for catalysis duringlyophilization through the addition of the targeted substrateprior to freezing. Moreover, the ligand may impede the for-mation of inactive Bmicroconformations^ in the active site(Aithal and Belur 2013). Bioimprinting methods can activatetannase remarkably offering a 100-fold increase of conversion(Nie et al. 2012b). Techniques such as pH tuning, interfacialactivation, and cryogenic protection have been applied (Nieet al. 2012a, 2014). Free tannases from Aspergillus species,
Table 2 Ferulic acid esterase-catalyzed reactions
Product Donor Acceptor Enzyme Solvent system Yield (time) T(°C)
Reference
1-Pentyl ferulate Ferulic acid 1-Pentanol FAEA CTAB: hexane:pentanol: buffer
60 % (n.q.) 40 Giuliani et al.2001
1-Butyl ferulate Methyl ferulate 1-Butanol CLEAsimmobilizedUltraflo L
Hexane: 1-butanol:buffer
97 % (144 h) 37 Vafiadi et al.2008a
1-Butyl sinapate Methyl sinapate 1-Butanol AnFaeA Hexane: 1-butanol:buffer
78 % (120 h) 35 Vafiadi et al.2008b
2-Butyl sinapate Methyl sinapate 2-Butanol AnFaeA Hexane: 2-butanol:buffer
9 % (120 h) 37 Vafiadi et al.2008a
1-Butyl caffeate Methyl caffeate 1-Butanol StFae-A Hexane: 1-butanol:buffer
Up to 25 % (144 h) 35 Topakas et al.2004
1-Butyl-p-coumarate Methyl p-coumarate 1-Butanol FoFae-I Hexane: 1-butanol:buffer
Up to 70 % (144 h) 35 Topakas et al.2003a
1-Propyl-p-hydroxyphenylacetate
p-Hydroxyphenylaceticacid
1-Propanol FoFae-II Hexane: 1-propanol: buffer
75 % (224 h) 30 Topakas et al.2003b
1-Propyl-p-hydroxylphenylpropio-nate
p-Hydroxylphenylpropio-nic acid
70 % (224 h)
Glycerol sinapate Sinapic acid Glycerol AnFaeA [C5OHmim][PF6]:buffer
76.7 % (24 h) 50 Vafiadi et al.2009Methyl sinapate Up to 7 % (120 h)
Glycerol ferulate Ferulic acid Glycerol FAE-PL Glycerol: DMSO:buffer
81 % (n.q.) 50 Tsuchiyamaet al. 2006
Diglycerol ferulates(mixture of isomers)
Ferulic acid Diglycerin S FAE-PL Diglycerin S:DMSO: buffer
95 % (12 h) 50 Kikugawa et al.2012
Glycerol p-coumarate p-Coumaric acid Glycerol FAE-PL Glycerol: DMSO:buffer
~60 % (72 h) 50 Tsuchiyamaet al. 2007
L-Arabinose ferulate Methyl ferulate L-Arabinose StFae-C Hexane: t-butanol:buffer
Up to 50 % (120 h) 35 Vafiadi et al.2005Ethyl ferulate 6.3 % (−)
D-Arabinose ferulate Methyl ferulate D-Arabinose Hexane: t-butanol:buffer
45 % (−) 35 Vafiadi et al.2007a
Ferulic acid D-Arabinose Multifect P3000 Hexane: 1-butanol:buffer
36.7 % (144 h) 35 Couto et al.2010D-Galactose ferulate Ferulic acid D-Galactose Depol 670 61.5 % (144 h)
D-Xylose ferulate Ferulic acid D-Xylose Hexane: 2-butanone:buffer
37.3 % (144 h)
Feruloyl raffinose Ferulic acid Raffinose Depol 740L Hexane: 2-butanone:buffer
11.9 % (7 days) 35 Couto et al.2011
Feruloyl galactobiose Ferulic acid Galactobiose Hexane: 1,4-dioxane:buffer
26.8 % (144 h)
Feruloyl xylobiose Ferulic acid Xylobiose Hexane: 2-butanone:buffer
9.4 % (144 h)Feruloyl arabinodiose Ferulic acid Arabinodiose 7.9 % (144 h)Feruloyl sucrose Ferulic acid Sucrose 13.2 % (n.q.)Feruloyl FOS Ferulic acid FOS 9.6 % (n.q.)
FAEA: FAE from Aspergillus niger; Ultraflo L, Depol 740L: multi-enzymatic preparation fromHumicola insolens; AnFaeA: type A FAE from A. niger;StFae-A, StFae-C: FAE from Sporotrichum thermophileATCC 34628; FoFae-I, FoFae-II: FAE from Fusarium oxysporum; FAE-PL: FAE from A. nigerpurified from the commercial preparation Pectinase PLBAmano^; Multifect P3000: multi-enzymatic preparation fromBacillus amyloliquefaciens; Depol670: multi-enzymatic preparation from Trichoderma reesei
Appl Microbiol Biotechnol
Penicillium variable, and Bacillus massiliensis (whole-cell)have synthesized propyl gallate in organic solvents (Yu andLi 2008; Sharma and Gupta 2003; Sharma and Saxena 2012;Beena et al. 2011). Regarding other galloyl esters, Toth andHensler (1952) reported the synthesis of methyl and ethylesters but not the phenyl ester of gallic acid in the presenceof tannase dissolved in buffer, revealing for the first time theability of soluble tannases to esterify. Gallic acid esters weresynthesized by an immobilized tannase from A. nigerperforming esterification of gallic acid with alcohols (C1–C12) and with several diols. This system proved that the en-zyme had broad specificity for alcohols but absolute specific-ity for the acid moiety (Weetall 1985).
Representing proanthocyanidin monomers, green tea cate-chins mainly compris ing of epicatechins (ECs) ,epigallocatechins (EGCs), epicatechin gallate (ECG), and epi-gallocatechin gallate (EGCG) have gained attention for theirstrong anti-oxidant and cardiovascular protective activity.Green tea is considered a useful agent for promoting skinregeneration or treatment for psoriasis, rosacea, and actinickeratosis and repairs UV-damaged skin in vivo, which leadsto the improvement of wrinkles (Hong et al. 2012). EGCG isan anti-inflammatory and anti-irritant anti-oxidant, which isresponsible for health benefits like the stimulation of collagenproduction while reducing oxidative damage within the skin.EGCG vehiculated in cosmetic formulations presents goodskin penetration and retention favoring its skin effects (dalBelo et al. 2009). Among epicatechin derivatives, EGC isthe most effective photoprotector, following in a descendingorder by EGCG, EC, and ECG (Hong et al. 2013). However, itis present in natural green tea preparations in low amountscompared to EGCG, which is the most abundant catechin ingreen tea (Cao and Ito 2004). Low-yield galloylation ofepicatechins has been achieved by an immobilized commer-cial tannase from A. niger in ionic liquids (Raab et al. 2007). Itis evident that tannases could be proved to be a powerfulbiocatalyst in order to modify the active constituents of greentea and synthesize tailor-made compounds with preferred bi-ological activities for use in different cosmeceutical products.High yield acetylation of catechin and ECGG has been report-ed using commercial lipases from R. miehei and P. cepacia(Lambusta et al. 1993; Zhu et al. 2014).
Proteases
Besides catalyzing the cleavage of peptide bonds for the pro-duction of peptide cosmeceuticals, proteases (EC 3.4) findapplication in transesterification reactions in organic solvents,lowering the cost of ester production and increasing reactionspecificity. Enzymes from different sources display differentfeatures; for example, contrary to serine proteases,the rmolys in ( a me ta l lo -p ro tease f rom Bac i l l usT
able3
Tannase-catalyzedreactio
ns
Product
Donor
Acceptor
Enzym
eSo
lvent
system
Yield
(tim
e)T(°C)
Reference
Methylg
allate
Gallic
acid
Methanol
Tannasefrom
Aspergillu
sniger
Hexane
90.7%
(8h)
50Sh
armaandSaxena
2012
Propyl
gallate
1-Propanol
94.8%
(8h)
Tannicacid
CNBr-agaroseim
mobilized
tannasefrom
Emericela
ridulans
Buffer
88%
(48h)
60–75
Goncalves
etal.2013
Methylg
allate
CNBr-agaroseim
mobilized
tannasefrom
Lactobacillus
plantarum
Buffer
55%
(−)
25Fernandez-Lorente
etal.2011
C1–C12
acyl
gallates
Gallic
acid
C1–C12
fatty
alcohols
Tannasefrom
Aspergillu
snigerim
mobilizedon
alkylaminosilanized
porous
silica
Solvent-free
10–95%
(18–48
h)RT
Weetall1985
C3–C5diol
gallates(strong
indicatio
nof
morethan
one
form
ofester)
Diols
50–80%
(24h)
Catechingallate
Gallic
acid
Catechin
Tannasefrom
Aspergillu
sniger
immobilizedon
EupergitC
[ΒMIM
][MEESO
4]:
buffer
1.3%
(20h)
RT
Raabetal.2007
Epicatechin
gallate
Epicatechin
5.4%
(20h)
Epigallo
catechin
gallate
Epigallo
catechin
3.1%
(20h)
Appl Microbiol Biotechnol
t h e rmopro t eo l y t i cu s ) i s no t gene r a l l y u sed intransesterifications (Pedersen et al. 2002). Studies haveproved that the S1 pocket of thermolysin active site can bindmedium and large hydrophobic amino acids, suggesting thatthe vinyl group can bind as well, allowing the possibility ofusing thermolysin for the synthesis of sugar esters. For thesereasons, the use of proteases for ester production in the cos-metic field is of great interest and potential (Fornbacke andClarsund 2013). The main compounds synthesized by prote-ases are summarized in Table 4.
As a typical flavonoid glycoside with anti-oxidant activity,rutin has been enzymatically esterified with different acyl do-nors to enhance its solubility and stability in lipophilic media.The regioselective transesterification of rutin with divinyl car-boxylates in pyridine was performed at 50 °C for 4 days by analkaline protease from B. subtilis (Xiao et al. 2005). Only 3″-O-substituted rutin ester was obtained in these conditionsshowing that regioselective acylation can be controlled byregulation of solvents and enzymes. Pre-irradiated alkalineprotease from B. subtilis increased transesterification oftroxerutin with divinyl dicarboxylates by 31 % in pyridineusing an ultrasound bath (150 W and 80 kHz) (Xiao et al.2011). Ultrasonic treatment is an environmentally benignmethod based on the cavitation phenomenon, which causesthe formation, expansion, and collapse of cavities generating
high temperatures and pressures of the neighboring surround-ings (Khan and Rathod 2015). Thus, cavitation can accelerateenzymatic reactions maintaining ambient conditions of theoverall environment. Ultrasonic treatment represents an effi-cient route of performing transterification in order to modifysolubility of anti-oxidant molecules.
Arbutin derivative with undecylenic acid located at its sug-ar moiety has been enzymatically synthesized using an alka-l i ne p ro t ease f rom B. sub t i l i s i n a mix tu re o fdimethylformamide and water (95:5) (Tokiwa et al. 2007a).The produced arbutin undecylenic acid ester showed to inhibitthe activity of tyrosinase from mushroom; in addition, thearbutin ester seemed to have high dermal absortion and didnot show the peculiar smell of undecylenic acid which com-monly prevents its application in cosmetics. Further studieshave proven that after 6 days of incubation of B16 melanomacells with arbutin undecylenic ester, melanin production levelswere decreased to approximately 30 % compared with that ofthe control cells (Tokiwa et al. 2007b). Alkaline protease fromB. subtilis was also applied in regioselective esterification ofthe hydroxyl group at C-7 position of kojic acid to producediverse lipophilic kojic acid esters in dimethylformamide(Raku and Tokiwa 2003). Kojic acid esters were effective asscavengers against DPPH radical, and they are expected toprevent oxidational stress in vivo. Moreover, their
Table 4 Protease-catalyzed reactions
Product Donor Acceptor Enzyme Solvent system Yield (time) T(°C)
Reference
7-O-Vinyl adipoyl kojicacid
Kojic acid Divinyl adipate Bioprase fromBacillussubtilis
Dimethylformamide 25 % (7 days) 30 Raku andTokiwa20037-O-Hexanoyl/octanoyl/
decanoyl kojic acidVinyl hexanoate/
octanoate/decanoate
13–27 %(7 days)
6-O-Undecylenoyl p-hydroxyphenyl β-D-glucopyranoside
Arbutin Undecylenic acidvinyl ester
Bioprase fromBacillussubtilis
Dimethylformamide 62 % (7 days) 40 Tokiwa etal.2007b
3″-O-Vinylsuccinyl orvinylsebacoyl-rutin
Rutin Divinyl succinate/sebacate
Subtilisin fromBacillussubtilis
Pyridine 12.8/19.8 %(4 days)
50 Xiao et al.2005
Vinylsuccinyl/vinylglutaryl/vinyladipoyl/dinylnonanedioyl/vinylsebacoyl/vinyltridecanedioyl-troxerutin
Troxerutin Divinyl succinate/glutarate/adipate/nonanedioate/sebacate/decanedioate
Subtilisin fromBacillussubtilis(-enzyme pre-irradiated)
Pyridine 10.6–33.10 %(4 h)
50 Xiao et al.2011
2-O-Lauroyl-sucrose Sucrose Vinyl laurate Alkalineprotease fromBacilluspseudofirmus
Dimethylformamide:pyridine 50–60 %(24 h)
45 Pedersenet al.2003
6-O-Vinyladipoyl-D-glucose/-D-mannose/-D-galactose/-methyl D-galactoside
D-Glucose/D-mannose/D-galactose/α-methyl D-galactoside
Divinyl adipate Alkalineprotease fromStreptomycessp.
Dimethylformamide 49–74 %(7 days)
35 Kitagawaet al.1999
Appl Microbiol Biotechnol
biodegradability exceeded 60 %, allowing their application incosmetics for the production of eco-friendly and oil-basedproduct products.
Transferases
A broad variety of bioactive glycosides has been synthesizedusing glycosyltransferases (GTFs; EC 2.4); enzymes that
catalyze the transfer of sugar moieties from an activated donorto specific acceptors forming glycosidic bonds. Novel EGCGmono- and di-glycosides with increased UV irradiation stabil-ity, browning resistance, and water solubility regardless of theposition or linkage of the glycosylation have been synthesizedby transferases from L. mesenteroides (Kitao et al. 1995;Moon et al. 2006a). EC mono-, di-, and tri-glycosides havebeen synthesized by a β-cyclodextrin glucosyltransferasefrom Paenibacillus sp. while various catechin derivatives by
Table 5 Transferase catalyzed reactions
Product Donor Acceptor Enzyme Solventsystem
Yield (time) T(°C)
Reference
EGCG glycosides (EGCG-G1,EGCG-G2A, EGCG-G2B)
Sucrose EGCG Glucansucrase fromLeuconostoc mesenteroides
Buffer 62.2 % (6.5 h) 28 Moon et al. 2006a
EC glycosides (EC3A, EC3B,EC3C, EC4A)
β-Cyclode-xtrin
(−)-Epicatechin
β-Cyclodextrin transferasefrom Paenibacillus sp.
Βuffer 18.1 % (24 h) 50 Aramsangtienchaiet al. 2011
Catechin 3′-O-α-D-glucopyranoside
Maltose (+)-Catechin Glycosyltransferase fromStreptococcus sobrinus
Buffer 13.7 % (24 h) 45 Nakahara et al.1995
Catechin 3′-O-α-D-glucopyranoside (main product)
Starch Cyclodextringlucanotransferase fromBacillus macerans
18.3 % (40 h) 40 Funayama et al.1993
Catechin 3′-O-α-D-glucopyranoside
Maltose Enzyme with transfer activityfrom Xanthomonascampestris WU-9701
57.1 % (36 h) 45 Sato et al. 2000
Hydroquinone fructoside Sucrose Hydroquinone Levansucrase fromLeuconostoc mesenteroides
Buffer 14 % (6 h) 28 Kang et al. 2009
β-Αrbutin-α-G1/β-arbutin-α-G2 Sucrose β-Arbutin Glucansucrase fromLeuconostoc mesenteroidesB-1299B
Buffer 27.1 % (10 h) 28 Moon et al. 2007a
Starch β-Arbutin Cyclomaltodextringlucanotransferase fromBacillus macerans
Buffer 70 % (16 h) 40 Sugimoto et al.2003
α-Αrbutin-α-G1/β-arbutin-α-G2 α-Arbutin Buffer 70 % (16 h) 40 Sugimoto et al.2005
α-Arbutin Sucrose Hydroquinone Amylosucrase fromDeinococcus geothermalis
Buffer 90 % (24 h) 35 Seo et al. 2012a
α-Arbutin (in a mixture ofproducts, G2–G7)
α-Cyclode-xtrin
Cyclodextrin glycosyltranferasefrom Thermoanaerobactersp. (Toruzyme 3.0 L; afteramyloglucosidase treatment)
Buffer 30.0 % (24 h) 40 Mathew andAdlercreutz2013
β-Arbutin-α-glycoside Sucrose β-Arbutin Amylosucrase fromDeinococcus geothermalisDSM 11300
Buffer 98 % (−) 35 Seo et al. 2009
Kojic acid glycosides (5-O-α-D-and 7-O-α-D-glucopyranoside)
Kojic acid Sucrose phosphorylase fromLeuconostoc mesenteroides
DMSO:buffer 19.7 % (24 h) 42 Kitao & Serine1994
Quercetin glycosides (3′-O-α-Dand 4-O-α-D glycopyranoside)
Quercetin Glucansucrase fromLeuconostoc mesenteroides
Acetone 23.1 % (5 h) 28 Moon et al. 2007b
Ampelopsin glycosides up to5 units(4′-O-α-D-glycopyranoside as mainproduct)
Ampelopsin Dextransucrase fromLeuconostoc mesenteroides
DMSO:buffer
87.3 % (1 h) 28 Woo et al. 2012
Astragalin glycosides (kaempferol-3-O-β-D-isomaltoside, 3-O-β-D-nigeroside, polymerized 3-O-β-D-isomaltooligosaccharides)
Sucrose Astragalin 24.5 % (5 h) 28 Kim et al. 2012
Ascorbic acid glycosides (2-O-α-D-glucopyranosyl L-ascorbicacid as main product)
α-Cyclode-xtrin
Ascorbic acid Cyclomaltodextringlucanotransferase formBacillus stearothermophilus
Buffer 45.6 % (1 h) 60 Aga et al. 1991
Benzoyl glycosides (1-O-benzoyl-α-D-, 2-O-benzoyl-α-D- and 2-O-benzoyl-β-D-glucopyranoside)
Sucrose Benzoic acid Sucrose phosphorylase fromStreptococcus mutans
Buffer 70 % (48 h) 37 Sugimoto et al.2007
Appl Microbiol Biotechnol
amylosucrases from Deinococcus geothermalis, Streptococcus sobrinus, a cyclodextrin glucanotransferase fromBacillus macerans and an enzyme with glycosyl transfer ac-tivity from Xanthomonas campestris (Aramsangtienchai et al.2011; Cho et al. 2011; Nakahara et al. 1995; Funayama et al.1993; Sato et al. 2000). Transferase-based modification ofhydroquinone has been focused on its glycosylation or theproduction of arbutin (α- and β-) glycosides. A two-step syn-thesis ofα-arbutin including prior treatment ofα-cyclodextrinwith an amyloglucosidase from A. niger and subsequent trans-fer reaction using a commercial cyclodextrin glucanotransferase from Thermoanaerobacter sp. has been reported(Mathew and Adlercreutz 2013). Before treatment, hydroqui-none was glycosylated with up to 7 glucose units while aftertreatment, α-arbutin was an absolute product. Results on thesynthesis of arbutin glycosides show that the α-glucosidiclinkage plays an important role in the inhibitory effect onhuman tyrosinase (Sugimoto et al. 2005).
2-O-α-D-glycopyranosyl L-ascorbic acid has been synthe-sized by a cyclomaltodextrin glucanotransferase fromBacillusstearothermophilus and a sucrose phosphorylase fromBifidobacterium longum (Aga et al. 1991; Kwon et al.2007). The first transglycosylation of CA was performed bya sucrose phosphorylase from B. longum in aqueous CO2
supercritical media resulting in the formation of caffeicmono- and di-glycosides (Shin et al. 2009). Ampelopsin is aflavonoid with numerous activities such as anti-inflammatory,anti-microbial, anti-oxidant, anti-hypertension, hepatoprotec-tive, anti-carcinogenic, anti-viral, and skin-whitening effects.A dextransucrase from L. mesenteroides synthesized a mix-ture of novel ampelopsin glycosides with up to 5 attachedglycoside units. The primary product, ampelopsin-4′-O-α-D-glucopyranoside, reached an optimal yield of 34 g/L while itshowed an 89-fold increase in water solubility, 14.5-fold in-crease in browning resistance comparing to ampelopsin, and
10-fold higher tyrosinase inhibition comparing to β-arbutin.Browning resistance was similar to ECGC glycosides andanti-oxidant activity superior to ampelopsin (Woo et al.2012). Another major flavonoid found in plants, astragalin,was modified by a dextransucrase from L. mesenteroides giv-ing products with increased inhibitory effects on matrixmetalloproteinase-1 expression, anti-oxidant effect, and mel-anin inhibition (Kim et al. 2012). Quercetin glycosides weresynthesized by a glucansucrase from L. mesenteroides show-ing increased water solubility, slower scavenging activity, andno improvement in tyrosinase inhibition (Moon et al. 2007b).Three main benzoyl and two main kojic acid glycosides weresynthesized by a sucrose phosphorylase from Streptococcusmutans and L. mesenteroides, respectively (Sugimoto et al.2007; Kitao and Serine 1994). Examples of transferase cata-lyzed reactions are presented in Table 5.
Glucosidases
Glucosidases, such as α- (EC 3.2.1.20) and β-glucosidases(EC 3.2.1.21), are a group of enzymes that hydrolyze individ-ual glucosyl residues from various glycoconjugates includingα- or β-linked polymers of glucose under physiological con-ditions. However, these enzymes are able to synthesize abroad variety of sugar derivatives under defined conditionsin two different manners: transglycosylation or reverse hydro-lysis (Park et al. 2005). Active compounds that have beenobtained by enzyme-catalyzed glucosidation include vitaminand arbutin derivatives as presented in Table 6.Pharmacological properties of vitamin E can be improved byincreasing its water solubility, absorbtivity and stabilitythrough glycosylation. A novel water-soluble vitamin E de-r ivat ive, 2-(α -D-glucopyranosyl)methyl-2 ,5,7,8-tetramethylchroman-6-ol (TMG) has been synthesized from
Table 6 Glucosidase-catalyzed reactions
Product Donor Acceptor Enzyme Solventsystem
Yield (time) T(°C)
Reference
4-Hydroxyphenyl-β-isomaltoside
Sucrose Arbutin α-Glucosidase fromSaccharomycescerevisiae
Buffer 50 % (20 h) 40 Milosavićet al.2007
Hydroquinone α-D-glucopyranoside
Maltose Hydroquinone α-Glucosidase fromSaccharomycescerevisiae
Buffer 13 % (20 h) 30 Prodanovićet al.2005Hydroquinone α-D-
isomaltoside15 % (20 h)
2-(α-D-Glucopyranosyl)methyl-2,5,7,8-tetramethylchroman-6-ol
Maltose 2-Hydroxymethyl-2,5,7,8-tetramethylchroman-6-ol(vitamin E derivative)
α-Glucosidase fromSaccharomyces sp.
DMSO (20 h) 40 Muraseet al.1998
β-D-Glucosyl-(1-6)-arbutin Cellobiose Arbutin β-Glucosidase fromThermotoganeapolitana
Buffer 2.8 % (12 h) 80 Jun et al.2008β-D-Glucosyl-(1-4)-arbutin
β-D-Glucosyl-(1-3)-arbutin
Appl Microbiol Biotechnol
2-hydroxymethyl-2,5,7,8-tetramethylchroman-6-ol (TM) andmaltose using α-glucosidase from Saccharomyces sp. in atransglycosylation reaction (Murase et al. 1998). Anti-oxidant activity of TMG was investigated on peroxidation ofphosphatidylcholine-liposomal (PC)-suspension, which isusually adopted as model for cellular biomembranes. TMGshowed higher efficacy on lipid peroxidation than ascorbicacid, when peroxidationwas provoked by lipid-soluble radicalgenerator such as 2,2′-azobis(2,4-dimethylvaleronitrile(AMVN). Moreover, TMG showed to inhibit cupric ion-induced peroxidation of (PC)-suspension and rat brain ho-mogenate while it delayed the generation of cholesteryl esterhydroperoxides when exposing human plasma to lipid orwater-soluble radical generators.
A β-glucosidase from Thermotoga neapolitana has syn-thesized arbutin-β-glycosides to be used as novel skin whit-ening agents (Jun et al. 2008).β-D-glucosyl-(1–3)-arbutin hasbeen proved to inhibit mushroom tyrosinase and it has beentested on B16F10 murine melanoma cell line showing thestrongest inhibitory effect on melanin synthesis in a dose-dependent manner without causing cytotoxicity. β-D-glucosyl-(1–3)-arbutin showed to be a more efficient inhibitorof melanin synthesis compared to arbutin. Similarly, arbutinhas been glycosyla ted by a α -glucosidase fromSaccharomyces cerevisiae to produce 4-hydroxyphenyl-β-isomaltoside (Milosavić et al. 2007), whose inhibitory capac-ity on tyrosinase is being investigated. α-Glucosidase fromS. cerevisiae also catalyzed the synthesis of hydroquinoneα-D-glucopyranoside and hydroquinone α-D-isomaltoside(Prodanović et al. 2005). Glycosylation of hydroquinone in-creased its water solubility and enhanced pharmaceuticalproperties such as skin whitening and anti-bacterial capacity.
Laccases
Laccases are dimeric or tetrameric glycosylated proteins,which usually bear four copper atoms per monomer distribut-ed in three redox sites (Gianfreda et al. 1999). These enzymesare able to catalyze the one-electron oxidation of phenols gen-erating phenoxy radicals and simultaneously reducing molec-ular dioxygen to water (Kudanga et al. 2011). Due to theirfeatures, including broad substrate specificity, catalysis in airwithout using H2O2, and production of water as only by-prod-uct, laccases are considered the ideal green catalysts. Besidescatalyzing catabolic and depolymerization processes, basedon reaction conditions, these enzymes can also carry out syn-thetic processes including the oxidization of aromatic com-pounds followed by heteromolecular coupling with co-substrates or simple oligomerization (Mikolasch and Schauer2009). The main compounds that have been synthesized bylaccase-catalyzed reactions include flavonoids, HCAs, and
other phenolics. Conditions of their production are describedin the following sections and summarized in Table 7.
The anti-oxidant activity of flavonoids derives from the B-ring, which is important for the H-transfer, and 2–3 doublebond ensuring electron delocalization. Moreover, in vitrostudies have demonstrated the importance of the 3-OH groupfor the anti-oxidant capacity. Rutin has been oxidized by alaccase from Myceliophtora thermophyla to produce flavo-noid polymers (Kurisawa et al. 2003a). The same result wasachieved by using Pycnoporus coccineus and Pycnoporussanguineus laccases as biocatalysts. Oxidized poly-rutinshowed enhanced anti-oxidant, anti-inflammatory, and anti-aging capacities compared to the rutin monomer (Uzan et al.2011). Enzymatic oxidation of catechin was also performedby a laccase from M. thermophyla producing poly-catechinwith greater superoxide scavenging and inhibitory capacityof xanthine oxidase (Kurisawa et al. 2003b). Laccase-catalyzed oxidation has been applied in order to enhance theanti-oxidant property of FA. Two dimeric products, β-5 andβ-β, were obtained by oxidation of FA in organic media usinga laccase from Trametes pubescens (Adelakun et al. 2012b).Reaction was performed in a biphasic system, as the concen-tration of ethyl acetate increased, and in monophasic systemusing dioxane or ethanol as co-solvents. The β-5 dimershowed higher anti-oxidant capacity than FA evaluated byDPPH and Trolox equivalent antioxidant capacity (TEAC)assays. Different oxidized products of HCAs were used toimprove anti-oxidant and anti-microbial activities of poly-mers, such as chitosan. A laccase from M. thermophyla wasused to functionalize chitosan with oxidated FA and ethyl-ferulate (Aljawish et al. 2012). Both derivatives showedhigher anti-oxidant activity than the substrates, especially theFA chitosan. The same strategy was applied to functionalizechitosan with CA using a laccase from Trametes versicolor,obtaining a functionalized polymer with higher anti-oxidantand anti-microbial activity than the substrates (Božič et al.2012b). These results indicated that the addition of an H-atom donating group, produced by laccase-mediatedoxidization, could generate a good chain breaking anti-oxi-dant. Laccase-mediated oxidation is proved to be a good strat-egy to develop functionalized polymers with enhanced anti-oxidant and anti-microbial activities.
Oxidation of tannic acid by a laccase from T. versicolorresulted in a variety of products including gallic acid, gallicacid dimers, partially gallic acid-esterified glucose, and glu-cose, while oxidation of quercetin offered an oligomericderivative (Božič et al. 2012a). Both oxidative products ofgallic acid and quercetin showed higher anti-oxidant activitythan the origin compounds. Furthermore, tannic acid orquercetin was used to functionalize chitosans by laccasewithout organic or acidic solvents. Both chitosan derivativesexhibited amplified radical scavenging ability and anti-microbial activity compared to the untreated chitosans. The
Appl Microbiol Biotechnol
laccase grafting method was also applicable to other pheno-lic compounds, as in the case of graft copolymers of starchwith lignosulfonates (Shogren and Biswas 2013). Enzymaticpolymerization of 8-hydroxyquinoline was achieved byusing a laccase from T. pubescens (Ncanana and Burton2007). Oxidization of 8-hydroxyquinoline was establishedto generate aromatic radicals which combined to form apolymeric product with a powerful anti-oxidant capacityand anti-radical efficiency. Laccase-mediated oxidizationwas also performed in organic solvents, due to their advan-tages as medium in biocatalysis. Oxidation of 2,6-dimethoxyphenol by T. versicolor laccase was investigated in bi-phasic or monophasic systems, leading the formation of adimeric product with anti-oxidant capacity twofold higherthan the substrate. The dimer production was increased inthe monophasic solvent using acetone as co-solvent, whileits production increased as the concentration of ethyl acetatewas increased to 90 % in the biphasic system. Organic sol-vents were also applied in the synthesis of resveratrol dimerscatalyzed by laccases from M. thermophyla andT. pubescens (Nicotra et al. 2004). M. thermophyla
laccase-catalyzed dimers were obtained in butanol saturatedwith buffer; and resveratrol dimers catalyzed byT. pubescens laccase were synthesized using a biphasic sys-tem of ethyl acetate and buffer. The products may serve aslead for the development of new drugs and as nutraceuticals,showing anti-oxidant activity comparable to resveratrol andits analogs.
Conclusions
A large variety of compounds with potential cosmeceuticalapplication can be obtained through biotechnological process-es. The reported examples of enzymatic synthesis or modifi-cation of natural compounds so far exploited highlight thepossibility of developing biologically active ingredients withanti-oxidant, anti-aging, anti-microbial, anti-wrinkling,photoprotective, or skin-whitening properties. The use of es-terases (such as lipases, feruloyl esterases, tannases), transfer-ases, glucosidases, proteases, and laccases allows the modifi-cation of target compounds under mild conditions,
Table 7 Laccase-catalyzed reactions
Product Donor Acceptor Enzyme Solvent system Yield (time) T(°C)
Reference
Caffeic acid-chitosan Caffeic acid Chitosan Laccase from Trametesversicolor
Phosphatebuffer
– (24 h) 30 Božič et al.2012aGallic acid-chitosan Gallic acid – (24 h)
Quercetin-chitosan Quercetin Chitosan – (24 h) Božič et al.2012bGallic acid-chitosan Tannic acid
Starch–sodiumlignosulfonate graftcopolymers
Sodiumlignosulfonate
Starch Sodium acetate – (4 h) 30 Shogren andBiswas2013
3,3,5,5-Tetramethoxybiphenyl-4,4-diol
2,6-Dimethoxyphenol
2,6-Dimethoxyphenol
Laccase from Trametespubescens
Ethyl acetate – (24 h) 28 Adelakunet al.2012a
Acetone – (24 h)
Ferulic acid dimers (5-β, β-β)
Ferulic acid Ferulic acid Ethyl acetate ordioxane orethanol
– (24 h) Adelakunet al.2012b
Poly 8-hydroxyquinoline
8-Hydroxyquinoline
8-Hydroxyquinoline
Acetone 76 % (24 h) 30 Ncanana andBurton2007
Resveratrol trans-dehydrodimer
Resveratrol Resveratrol Ethyl acetate 18 % (4 days) 45 Nicotra et al.2004Laccase from Myceliophtora
thermophyla (supported onglass beads)
n-Butanol 31 % (4 days)
Ethyl-ferulate-chitosan
Ethyl ferulate Chitosan Laccase from Myceliophtorathermophyla
Phosphatebuffer
(4 h) 30 Aljawishet al. 2012
Ferulic acid-chitosan Ferulic acid (4 h)Poly-catechin (+) - Catechin (+) - Catechin Acetone 95 % (24 h) RT Kurisawa
et al.2003b
Poly-rutin Rutin Rutin Methanol 79 % (24 h) RT Kurisawaet al.2003a
Oligorutin Rutin Rutin Laccase from Pycnoporuscoccineus
Glycerol/ethanol/buffer
67 % (24 h) RT Uzan et al.2011
Laccase from Pycnoporussanguineus
Appl Microbiol Biotechnol
maintaining their biological activity and avoiding the forma-tion of by-products. These advantages fit the increasing de-mand for natural cosmetics, boosting eco-friendly design andproduction of active compounds in order to replace chemicalprocesses currently used.
Acknowledgments This work was supported by grant from EuropeanUnion—Large-scale integrating project targeted to SMEs BOptimizedesterase biocatalysts for cost-effective industrial production(OPTIBIOCAT)^ grant agreement no. 613868, co-funded within theFP7 Knowledge Based Bio-Economy (KBBE).
Compliance with ethical standards
Funding This study was funded by grant from European Union Grantagreement no. 613868.
Conflict of interest The authors declare that they have no conflict ofinterest.
Ethical approval This article does not contain any studies with humanparticipants or animals performed by any of the authors.
Open Access This article is distributed under the terms of the CreativeCommons At t r ibut ion 4 .0 In te rna t ional License (h t tp : / /creativecommons.org/licenses/by/4.0/), which permits unrestricted use,distribution, and reproduction in any medium, provided you give appro-priate credit to the original author(s) and the source, provide a link to theCreative Commons license, and indicate if changes were made.
References
Adelakun OE, Kudanga T, Green IR, le Roes-Hill M, Burton SG (2012a)Enzymatic modification of 2, 6-dimethoxyphenol for the synthesisof dimers with high antioxidant capacity. Process Biochem 47:1926–1932. doi:10.1016/j.procbio.2012.06.027
Adelakun OE, Kudanga T, Parker A, Green IR, le Roes-Hill M, BurtonSG (2012b) Laccase-catalyzed dimerization of ferulic acid amplifiesantioxidant activity. J Mol Catal B Enzym 74:29–35. doi:10.1016/j.molcatb.2011.08.010
Aga H, Yoneyama SS, Yamamoto I (1991) Synthesis of 2-O-α-d-glucopyranosyl L-ascorbic acidby cyclomal todextr inglucanotransferase from Bacillus stearothermophilus. Agric BiolChem 55:1751–1756. doi:10.1080/00021369.1991.10870856
Aithal M, Belur PD (2013) Enhancement of propyl gallate yield innonaquous medium using novel cell associated tannase of Bacillusmassiliensis. Prep Biochem Biotechnol 43:445–455. doi:10.1080/10826068.2012.745873
Ajima A, Takahashi K, Matsushima A, Saito Y, Inada Y (1986) Retinylesters synthesis by polyethylene glycol-modified lipase in benzene.Biotechnol Lett 8:547–552
Aljawish A, Chevalot I, Piffaut B, Rondeau-Mouro C, Girardin M,Jasniewski J, Schera J, Muniglia L (2012) Functionalization of chi-tosan by laccase-catalyzed oxidation of ferulic acid and ethylferulate under heterogeneous reaction conditions. CarbohydrPolym 87:537–544. doi:10.1016/j.carbpol.2011.08.016
Almeida VM, Branco CRC, Assis SA, Vieira IJC, Braz-Filho R, BrancoA (2012) Synthesis of naringin 6"-ricinoleate using immobilizedlipase. Chem Cent J 6:41. doi:10.1186/1752-153X-6-41
Andersen A, Bergfeld WF, Belsito DV, Hill RA, Klaassen CD, LieblerDC, Marks JG, Shank RC, Slaga TJ, Snyder PW (2010) Finalamended safety assessment of hydroquinone as used in cosmetics.Int J Toxicol 29:2745–2875. doi:10.1177/1091581810385957
Zondlo Fiume M (2002) Final report on the safety assessment of tocoph-erol, tocopheryl acetate, tocopheryl linoleate, tocopheryl linoleate/oleate, tocopheryl nicotinate, tocopheryl succinate, dioleyltocopheryl methylsilanol, potassium ascorbyl tocopherol phosphate,and tocophersolan. Int J Toxicol 21:51–116
Aramsangtienchai P, Chavasiri W, Ito K, Pongsawasdi P (2011) Synthesisof epicatechin glucosides by a β-cyclodextrin glycosyltransfesrase.JMol Catal B Enzym73:27–34. doi:10.1016/j.molcatb.2011.07.013
Ardhaoui M, Falcimaigne A, Engasser JM, Moussou P, Pauly G, GhoulM (2004b) Acylation of natural flavonoids using lipase of Candidaantarctica as biocatalyst. J Mol Catal B Enzym 29:63–67. doi:10.1016/j.molcatb.2004.02.013
Ardhaoui M, Falcimaigne A, Ognier S, Engasser JM, Moussou P, PaulyG, Ghoul M (2004a) Effect of acyl donor chain length and substitu-tions pattern on the enzymatic acylation of flavonoids. J Biotechnol110:265–271. doi:10.1016/j.jbiotec.2004.03.003
Ashari SE, Mohamad R, Ariff A, Basir M, Salleh AB (2009)Optimization of enzymatic synthesis of palm-based kojic acid esterusing response surface methodology. J Oleo Sci 58:503–510
Battestin V, Macedo GA, De Freitas VAP (2008) Hydrolysis of epigallo-catechin gallate using a tannase from Paecilomyces variotii. FoodChem 108:228–233. doi:10.1016/j.foodchem.2007.10.068
Beena PS, Basheer SM, Bhat SG, Bahkali AH, ChandrasekaranM (2011)Propyl gallate synthesis using acidophilic tannase and simultaneousproduction of tannase and gallic acid by marine Aspergillusawamori BTMFW032. Appl Biochem Biotechnol 164:612–628.doi:10.1007/s12010-011-9162-x
Bouaziz A, Horchani H, Salem NB, Chaari A, Chaabouni M, Gargouri Y,Sayari A (2010) Enzymatic propyl gallate synthesis in solvent-freesystem: optimization by response surface methodology. J Mol CatalB Enzym 67:242–250. doi:10.1016/j.molcatb.2010.08.013
Bousquet MP, Willemot RM, Monsan P, Boures E (1999) Enzymaticsynthesis of α-butyl glycoside lactate: a new α-hydroxy acid deriv-ative. Biotechnol Bioeng 62:225–234
Božič M, Gorgieva S, Kokol V (2012a) Laccase-mediatedfunctionalization of chitosan by caffeic and gallic acids for modu-lating antioxidant and antimicrobial properties. Carbohydr Polym87:2388–2398. doi:10.1016/j.carbpol.2011.11.006
Božič M, Gorgieva S, Kokol V (2012b) Homogeneous and heteroge-neous methods for laccase-mediated functionalization of chitosanby tannic acid and quercetin. Carbohydr Polym 89:854–864. doi:10.1016/j.carbpol.2012.04.021
Bradoo S, Saxerna RK, Gupta R (1999) High yields of ascorbyl palmitateby thermostable lipase-mediated esterification. JAOCS 76:1291–1295
Brandt FS, Cazzaniga A, Hann M (2011) Cosmeceuticals: current trendsand market analysis. Semin Cut Med Surg 1:141–143. doi:10.1016/j.sder.2011.05.006
Burham H, Rasheed RAGA, Noor NM, Badruddin S, Sidek H (2009)Enzymatic synthesis of palm-based ascorbyl esters. J Mol Catal BEnzym 58:153–157. doi:10.1016/j.molcatb.2008.12.012
Cao X, Ito Y (2004) Preparation and purification of epigallocatechin byhigh-speed countercurrent chromatography (HSCC). J LiqChromatogr Relat Technol 27:145–152. doi:10.1081/JLC-120027091
Chandel C, Kumar A, Kanwar SS (2011) Enzymatic synthesis of butylferulate by silica-immobilized lipase in non-aqueous medium. JBiomed Nanotechnol 2:400–408. doi:10.4236/jbnb.2011.24049
Chebil L, Anthoni J, Humeau C, Gerardin C, Engasser JM, Ghoul M(2007) Enzymatic acylation of flavonoids: effect of the nature ofthe substrate, origin of lipase and operating conditions on conver-sion yield and regioselectivity. J Agric Food Chem 55:9496–9502.doi:10.1021/jf071943j
Appl Microbiol Biotechnol
Chen B, Liu H, Guo Z, Huang J, Wang M, Xu X, Zheng L (2011b)Lipase-catalyzed esterification of ferulic acid with oleyl alcohol inionic liquid/isooctane binary systems. J Agric Food Chem 59:1256–1263. doi:10.1021/jf104101z
Chen CS, Liu KJ, Lou YH, Shieh CJ (2002) Optimization of kojic acidmonolaurate synthesis with lipase PS from Pseudomonas cepacia. JSci Food Agric 82:601–605. doi:10.1002/jsfa.1083
Chen HC, Chen JH, Chang C, Shieh CJ (2011a) Optimization ofultrasound-accelerated synthesis of enzymatic caffeic acid phenethylester by response surface methodology. Ultrason Sonochem 18:455–459. doi:10.1016/j.ultsonch.2010.07.018
Chen HC, Twu YK, Chang CMJ, Liue YC, Shieh CJ (2010) Optimizedsynthesis of lipase-catalyzed octyl caffeate by Novozym® 435. IndCrop Prod 32:522–526. doi:10.1016/j.indcrop.2010.06.028
Chigorimbo-Murefu NTL, Riva S, Burton SG (2009) Lipase-catalysedsynthesis of esters of ferulic acid with natural compounds and eval-uation of their antioxidant properties. J Mol Cat: Enzym B 56:277–282. doi:10.1016/j.molcatb.2008.05.017
Cho HK, Kim HH, Seo DH, Jung JH, Park JH, Baek NI, Kim MJ, YooSH, Cha J, Kim YR, Park CS (2011) Biosynthesis of (+)-catechinglycosides using recombinant amylosucrase from Deinococcusgeothermalis DSM 11300. Enzym Microb Technol 49:246–253.doi:10.1016/j.enzmictec.2011.05.007
Choi CM, Berson DS (2006) Cosmeceuticals. Semin CutanMed Surg 25:163–168
Ciftci D, Saldana MDA (2012) Enzymatic synthesis of phenolic lipidsusing flaxseed oil and ferulic acid in supercritical carbon dioxidemedia. J Supercrit Fluids 72:255–262. doi:10.1016/j.supflu.2012.09.007
Compton DL, Laszlo (2009) 1,3-Diferuloyl-sn-glycerol from the biocat-alytic transesterification of ethyl-4-hydroxy-3-methoxy cinnamicacid (ethyl ferulate) and soybean oil. Biotechnol Lett 31:889–896
Compton DL, Laszlo JA, BerhowMA (2000) Lipase-catalyzed synthesisof ferulate esters. JAOCS 77:513–519
Cosmetic Ingredient Review (1987) Final report on the safety assessmentof retinyl palmitate and retinol. J Am Coll Toxicol 6:279–320. doi:10.3109/10915818709098562
Cosmetic International Review (2007) Final report on the amended safetyassessment of propyl gallate. Int J Toxicol 26:89–118. doi:10.1080/10915810701663176
Costa ICR, Sutili FK, da Silva GVV, Leite SGF, Miranda LSM, de SouzaROMA (2014) Lipase catalyzed ascorbyl palmitate synthesis undermicrowave irradiation. J Mol Catal B Enzym 102:127–131. doi:10.1016/j.molcatb.2014.02.002
Couto J, Karboune S, Mathew R (2010) Regioselective synthesis offeruloylated glycosides using the feruloyl esterase expressed in se-lected commercial multi-enzymatic preparations as biocatalysts.Biocatal Biotransfor 28:235–244. doi:10.3109/10242422.2010.493209
Couto J, St-Louis R, Karboune S (2011) Optimization of feruloylesterase-catalyzed synthesis of feruloylated oligosaccharides by re-sponse face methodology. J Mol Catal B Enzym 73:53–62. doi:10.1016/j.molcatb.2011.07.016
Cui FJ, Zhao HX, Sun WJ, Wei Z, Yu SL, Zhou Q, Dong Y (2013)Ultrasound-assisted lipase-catalyzed synthesis of D-isoascorbyl pal-mitate: process optimization and kinetic evaluation. Chem Cent J 7:180. doi:10.1186/1752-153X-7-180
Dal Belo SE, Gaspar LR, Maia Campos PMBG, Marty JP (2009) Skinpenetration of epigallocatechin-3-gallate and quercetin from greentea and ginkgo biloba extracts vehiculated in cosmetic formulations.Skin Pharmacol Physiol 22:299–304. doi:10.1159/000241299
De Araujo MEMB, Contesini FJ, Franco YEM, Sawaya ACHF, AlberotTG, Dalfre N, Carvalho RO (2011) Optimized enzymatic synthesisof hesperidin fatty acid esters in a two-phase system containing ionicliquid. Molecules 16:7171–7182. doi:10.3390/molecules16087171
De Oliveira EB, Humeau C, Chebil L, Maia ER, Dehez F, Maigret B,Ghoul M, Engasser JM (2009) A molecular modeling study to ra-tionalize the regioselectivity in acylation of flavonoid glycosidescatalyzed by Candida antarctica lipase B. J Mol Catal B Enzym59:96–105. doi:10.1016/j.molcatb.2009.01.011
Duan Y, Du Z, Yao Y, Li R, Wu D (2006) Effect of molecular sieves onlipase-catalyzed esterification of rutin with stearic acid. J Agric FoodChem 54:6219–6225
El-Boulifi N, Ashari SE, Serrano M, Aracil J, Martinez M (2014)Solvent-free lipase-catalyzed synthesis of a novel hydroxyl-fattyacid derivative of kojic acid. Enzym Microb Technol 55:128–132.doi:10.1016/j.enzmictec.2013.10.009
Enaud E, Humeau C, Piffaut B, Girardin M (2004) Enzymatic synthesisof new aromatic esters of phloridzin. J Mol Catal B Enzym 27:1–6.doi:10.1016/j.molcatb.2003.08.002
Fadnavis NW, Babu RL, Vadivel SK, Deshpande AA, Bhalerao UT(1998) Lipase catalyzed regio- and stereospecific hydrolysis:chemoenzymatic synthesis of both (R)- and (S)-enantiomers of a-lipoic acid. Tetrahedron Asymmetry 9:4109–4112. doi:10.1016/S0957-4166(98)00447-9
Fernandez-Lorente G, Bolivar JM,Martin JR, Curiel JA, Munoz R, de lasRivas B, Carrascosa AV, Guisan JM (2011) Synthesis of propylgallate by transesterification of tannic acid in aqueous media cata-lyzed by immobilized derivatives of tannase from Lactobacillusplantarum. Food Chem 128:214–217. doi:10.1016/j.foodchem.2011.02.057
Form M, Adlercreutz P, Mattiasson B (1997) Lipase catalyzed esterifica-tion of lactic acid. Biotechnol Lett 19:315–317
FornbackeM, ClarsundM (2013) Cold-adapted proteases as an emergingclass of therapeutics. Infect Dis Ther 2:15–26. doi:10.1007/s40121-013-0002-x
Funayama M, Nishino T, Hirota A, Murao S, Takenishi S, Nakano H(1993) Enzymatic synthesis of (+)catechin-a-glucoside and its effecton tyrosinase activity. Biosci Biotechnol Biochem 57:1666–1669.doi:10.1271/bbb.57.1666
Gazak R, Marhol P, Purchartova K, Monti D, Biedermann D, Riva S,Cvak L, Kren V (2010) Large-scale separation of silybin diastereo-isomers using lipases. Process Biochem 45:1657–1663. doi:10.1016/j.procbio.2010.06.019
Gianfreda L, Xu F, Bollag JM (1999) Laccases: a useful group ofoxidoreductive enzymes. Biorem J 3:1–26. doi:10.1080/10889869991219163
Giuliani S, Piana C, Setti L, Hochkoeppler A, Pifferi PG,Williamson PG,Faulds CB (2001) Synthesis of pentylferulate by a feruloyl esterasefrom Aspergillus niger using water-in-oil microemulsions.Biotechnol Lett 23:325–330
Goncalves HB, Jorge JA, Pessela BC, Fernanzed Lorente G, Guisan JM,Guimaraes LHS (2013) Characterization of a tannase fromEmericela nidulans immobilized on ionic and covalent supportsfor propyl gallate synthesis. Biotechnol Lett 35:591–598. doi:10.1007/s10529-012-1111-4
Gulati R, Saxena RK, Gupta R, Yadav RP, Davidson S (1999) Parametricoptimisation of Aspergillus terreus lipase production and its poten-tial in ester synthesis. Process Biochem 35:459–464. doi:10.1016/S0032-9592(99)00090-4
Ha SH, Van Anh T, Lee SH, Koo M (2012) Effect of ionic liquids onenzymatic synthesis of caffeic acid phenethyl ester. BioprocessBiosyst Eng 35:235–240. doi:10.1007/s00449-011-0601-4
Hasegawa S, Azuma M, Takahashi K (2008) Enzymatic esterification oflactic acid, utilizing the basicity of particular polar organic solventsto suppress acidity of lactic acid. J Chem Technol Biotechnol 83:1503–1510. doi:10.1002/jctb.1935
Hassan MA, Ismail F, Yamamoto S, Yamada H, Nakanishi K (1995)Enzymatic synthesis of galactosylkojic acid with immobilized b-galactosidase from Bacillus circulans. Biosci Biotechnol Biochem59:543–545. doi:10.1271/bbb.59.543
Appl Microbiol Biotechnol
HongYH, Jung EY, Shin KS, KimTY, YuKW, Chang UJ, SuhHJ (2012)Photoprotective effects of a formulation containing tannase-converted green tea extract against UVB-induced oxidative stressin hairless mice. Appl Biochem Biotechnol 166:165–175. doi:10.1007/s12010-011-9413-x
Hong YH, Jung EY, Shin KS, Yu KW, Chang UJ, Suh HJ (2013)Tannase-converted green tea catechins and their anti-wrinkle activ-ity in humans. J Cosmet Dermatol 12:137–143. doi:10.1111/jocd.12038
Hsieh HJ, Nair GR, Wu WT (2006) Production of ascorbyl palmitate bysurfactant-coated lipase in organic media. J Agric Food Chem 54:5777–5781
Ishihara K, Nishimura Y, Kubo T, Okada C, Hamada H, Nakajima N(2002) Enzyme-catalyzed acylation of plant polyphenols for inter-pretation of their functions. Plant Biotechnology 19:211–214. doi:10.5511/plantbiotechnology.19.211
Ishihara K, Katsube Y, Kumazawa N, Kuratani M, Masuoka N, Nakajima N(2010) Enzymatic preparation of arbutin derivatives: lipase-catalyzeddirect acylation without the need of vinyl ester as an acyl donor. JBiosci Bioeng 109:554–556. doi:10.1016/j.jbiosc.2009.11.009
Jakovetic SM, Jugovic BZ, Gvozdenovic MM, Bezbradica DJI, AntovMG, Mijin DZ, Knezevic-Jugovic ZD (2013) Synthesis of aliphaticesters of cinnamic acid as potential lipophilic antioxidants catalyzedby lipase B from Candida antarctica. Appl Biochem Biotechnol170:1560–1573. doi:10.1007/s12010-013-0294-z
Jiang XJ, Hu Y, Jiang L, Gong JH, Huang H (2013) Synthesis of vitaminE succinate from Candida rugosa lipase in organic medium. ChemRes Chin Univ 29:223–226. doi:10.1007/s40242-013-2486-z
Jun SY, Park KM, Choi KW, JangMK, Kang HY, Lee SH, Park KH, ChaJ (2008) Inhibitory effects of arbutin-β-glycosides synthesized fromenzymatic transglycosylation for melanogenesis. Biotechnol Lett30:743–748. doi:10.1007/s10529-007-9605-1
Kaki SS, Grey C, Adlercreutz P (2012) Bioorganic synthesis, character-ization and antioxidant activity of esters of natural phenolics and α-lipoic acid. J Biotechnol 157:344–349. doi:10.1016/j.jbiotec.2011.11.012
Kang J, Kim YM, Kim N, Kim DW, Nam SH, Kim D (2009) Synthesisand characterization of hydroquinone fructoside using Leuconostocmesenteroides levansucrase. Appl Microbiol Biotechnol 83:1009–1016. doi:10.1007/s00253-009-1936-5
Katsoura MH, Polydera AC, Katapodis P, Kolisis FN, Stamatis H (2007)Effect of different reaction parameters on the lipase-catalyzed selec-tive acylation of polyhydroxylated natural compounds in ionic liq-uids. Process Biochem 42:1326–1334. doi:10.1016/j.procbio.2007.07.004
Katsoura MH, Polydera AC, Tsironis L, Tselepis AD, Stamatis H (2006)Use of ionic liquids as media for the biocatalytic preparation offlavonoid derivatives with antioxidant potency. J Biotechnol 123:491–503. doi:10.1016/j.jbiotec.2005.12.022
Khamaruddin NH, Basri M, Lian GEC, Salleh AB, Abdul-RahmanRNZR, Ariff A, Mohamad R, Awang R (2008) Enzymatic synthesisand characterization of palm-based kojic acid ester. J Oil Palm Res20:461–469
Khan NR, Rathod VK (2015) Enzyme catalyzed synthesis of cosmeticesters and its intensification: a review. Process Biochem 50:1793–1806. doi:10.1016/j.procbio.2015.07.014
Khmelnitsky YL, Hilhorst R, Veeger C (1988) Detergentlessmicroemulsions as media for enzymatic reactions. Eur J Biochem176:265–271
Kidwai M, Mothsra P, Gupta N, Jumar SS, Gupta R (2009) Green enzy-matic synthesis of L-ascorbyl fatty acid ester: an antioxidant. SynthCommun 39:1143–1151. doi:10.1080/00397910802513045
Kikugawa M, Tsuchiyama M, Kai K, Sakamoto T (2012) Synthesis ofhighly water-soluble feruloyl diglycerols by esterification of anAspergillus niger feruloyl esterase. Appl Microbiol Biotechnol 95:615–622. doi:10.1007/s00253-012-4056-6
Kim GE, Kang HK, Seo ES, Jung SH, Park JS, Kim DH, Kim DW, AhnSA, Sunwoo C, Kim D (2012) Glucosylation of the flavonoid,astragalin by Leuconostoc mesenteroides B-512FMCMdextransucrease acceptor reactions and characterization of the prod-ucts. Enzym Microb Technol 50:50–56. doi:10.1016/j.enzmictec
Kim SK, Wijesekara I (2012) Chapter 1. Cosmeceuticals from marineresources: prospects and commercial trends. In: Kim S-K (ed)Marine cosmeceuticals—trends and prospects. CRC Press, Taylor& Francis Group, New York ISBN 9781439860281
Kiran KR, Divakar S (2001) Lipase catalyzed synthesis of organic acidesters of lactic acid in non-aqueous media. J Biotechnol 87:109–121. doi:10.1016/S0168-1656(01)00242-5
Kitagawa M, Fan H, Raku T, Shibatani S, Maekawa Y, Hiraguri Y, et al.(1999) Selective enzymatic preparation of vinyl sugar esters usingDMSO as a denaturing co-solvent. Biotechnol Lett 21:355–359. doi:10.1023/A:1005451009804
Kitao S, Matsudo T, Saitoh M, Horiuchi T, Sekine H (1995) Enzymaticsyntheses of two stable (−)-epigallocatechin gallate-glucosides bysucrose phosphorylase. Biosci Biotechnol Biochem 59:2167–2169. doi:10.1271/bbb.59.2167
Kitao S, Sekine H (1994) a-D-glycosyl transfer of phenolic compoundsby sucrose phosphorylase from Leuconostoc mesenteroides and pro-duction of a-arbutin. Biosci Biotechnol Biochem 58:38–42. doi:10.1271/bbb.58.38
Kitao S, Serine H (1994) Syntheses of two kojic acid glucosides withsucrose phosphorylase from Leuconostoc mesenteroides. BiosciBiotechnol Biochem 58:419–420. doi:10.1271/bbb.58.419
Kobayashi T, Adachi S, Nakanishi K, Matsuno R (2001) Semi-continuous production of lauroyl kojic acid through lipase-catalyzed condensation in acetonitrile. J Biochem Eng 9:85–89.doi:10.1016/S1369-703X(01)00129-2
Kudanga T, Nyanhongo GS, Guebitz GM, Burton S (2011) Potentialapplications of laccase-mediated coupling and grafting reactions: areview. Enzym Microb Technol 48:195–208. doi:10.1016/j.enzmictec.2010.11.007
Kurata A, Takemoto S, Fujita T, Iwai K, Furusawa M, Kishimoto N(2011) Synthesis of 3-cyclohexylpropyl caffeate from 5-caffeoylquinic acid with consecutive enzymatic conversions in ionicliquid. J Mol Catal B Enzym 69:161–167. doi:10.1016/j.molcatb.2011.01.012
Kurisawa M, Chung J, Uyama H, Kobayashi S (2003a) Laccase-catalyzed synthesis and antioxidant property of poly (catechin).Macromol Biosci 3:758–764. doi:10.1002/mabi.200300038
Kurisawa M, Chung JE, Uyama H, Kobayashi S (2003b) Enzymaticsynthesis and antioxidant propert ies of poly (rut in) .Biomacromoles 4:1394–1399. doi:10.1021/bm034136b
Kwon T, Kim CT, Lee JH (2007) Transglycosylation of ascorbic acid toascorbic acid 2-glucoside by a recombinant sucrose phosphorylasefeorm Bifidobacterium longum. Biotechnol Lett 29:611–615. doi:10.1007/s10529-006-9285-2
Lajis AFB, Basir M, Mohamad R, Hamid M, Ashari SE, Ishak N,Zookiflie A, Ariff AB (2013) Enzymatic synthesis of kojic acidesters and their potential industrial applications. Chem Pap 67:573–585. doi:10.2478/s11696-013-0336-6
Lajis AFB, Hamid M, Ariff AB (2012) Depigmenting effect of kojic acidesters in hyperpigmented B16F1 melanoma cells. J BiomedBiotechnol 2012:952452. doi:10.1155/2012/952452
Lambusta D, Nicolosi G, Patty A, Piattelli M (1993) Enzyme mediatedregioprotection-deprotection of hydroxyl groups in (+)-catechin.Synthesis 11:1155–1158. doi:10.1055/s-1993-26019
Laszlo JA, Compton DL (2006) Enzymatic glycerolysis andtransesterification of vegetable oil for enhanced production offeruloylated glycerols. JAOCS 83:765–770
Lee HJ, Kim JW (2012) Anti-inflammatory effects of arbutin inlipopolysaccharide-stimulated BV2 microglial cells. Inflamm Res61:817–825. doi:10.1007/s00011-012-0474-02
Appl Microbiol Biotechnol
Li W, Wu H, Liu B, Hou X, Wan D, Lou W, Zhao J (2015) Highlyefficient and regioselective synthesis of dihydromyricetinesters byimmobilized lipase. J Biotechnol 199:31–37. doi:10.1016/j.jbiotec.2015.02.012
Liu KJ, Shaw JF (1998) Lipase-catalyzed synthesis of kojic acid esters inorganic solvents. JAOCS 75:1507–1511
Liu L, PangM, ZhangY (2015) Lipase-catalyzed regioselective synthesisof flavone C-glucosides esters and high-efficiency oil-soluble anti-oxidant of bamboo leaves. Eur J Lipid Sci Technol 117:1636–1646.doi:10.1002/ejlt.201400541
Liu ZQ, Zheng XB, Zhang SP, Zheng YG (2012) Cloning, expressionand characterization of a lipase gene from the Candida antarcticaZJB09193 and its application in biosynthesis of vitamin A esters.Microbiol Res 167:452–460. doi:10.1016/j.micres.2011.12.004
Lue BM, Guo Z, Xu X (2010) Effect of room temperature ionic liquidstructure on the enzymatic acylation of flavonoids. Process Biochem45:1375–1382. doi:10.1016/j.procbio.2010.05.024
Luo XP, Du LH, He F, Zhou CH (2013) Controllable regioselective ac-ylation of flavonoids catalyzed by lipase in microreactors. JCarbohydr Chem 32:450–462. doi:10.1080/07328303.2013.843095
Lv LX, Chen SY, Li YQ (2008) Study of lipase-catalysed synthesis ofascorbyl benzoate in cyclohexanone using response surface meth-odology. J Sci Food Agric 88:659–666. doi:10.1002/jsfa.3132
Maczurek A, Hager K, Kenklies M, Sharman M, Martins R, Engel J,Carlson DA, Munch G (2008) Lipoic acid as an anti-inflammatoryand neuroprotective treatment for Azheimer’s disease. Adv DrugDeliv Rev 60:1463–1470. doi:10.1016/j.addr.2008.04.015
Mathew S, Adlercreutz P (2013) Regioselective glycosylation of hydro-quinone to α-arbutin by cyclodextrin glucanotransferase fromThermoanaerobacter sp. Biochem Eng J 79:187–193. doi:10.1016/j.bej.2013.08.001
Matsuo T, Kobayashi T, Kimura Y, Hosoda A, Taniguchi H, Adachi S(2008) Continuous synthesis of glyceryl ferulate using immobilizedCandida antarctica lipase. J Oleo Sci 57:375–380
Maugard T, Legoy MD (2000) Enzymatic synthesis of derivatives ofvitamin A in organic media. J Mol Catal B Enzym 8:275–280.doi:10.1016/S1381-1177(99)00078-8
Mbatia B, Kaki SS, Mattiasson B, Mulla F, Adlercreutz P (2011)Enzymatic synthesis of lipophilic rutin and vanillyl esters from fishbyproducts. J Agric Food Chem 59:7021–7027. doi:10.1021/jf200867r
Mellou F, Lazari D, Skaltsa H, Tselepis AD, Kolisis FN, Stamatis H(2005) Biocatalytic preparation of acylated derivatives of flavonoidglycosides enhances their antioxidant and antimicrobial activity. JBiotechnol 116:295–304
Mellou F, Loutrari H, Stamatis H, Roussos C, Kolisis FN (2006)Enzymatic esterification of flavonoids with unsaturated fatty acids:effect of the novel esters on vascular endothelial growth factor re-lease from K562 cells. Process Biochem 41:2029–2034. doi:10.1016/j.procbio.2006.05.002
Mikolasch A, Schauer F (2009) Fungal laccases as tools for the synthesisof new hybrid molecules and biomaterials. Appl MicrobiolBiotechnol 82:605–624. doi:10.1007/s00253-009-1869-z
Milisavljecic A, Stojanovic M, Carevic M, Mihailovic M, Velickoviz D,Milosavic N, Bezbradica D (2014) Lipase-catalyzed esterification ofphloridzin: acyl donor effect on enzymatic affinity and antioxidantproperties of esters. Ind Eng Chem Res 53(43):16644–16651. doi:10.1021/ie5027259
Milosavić NB, Prodanović RM, Jankov RM (2007) A simple and effi-cient one-step, regioselective, enzymatic glucosylation of arbutin byα-glucosidase. Tetrahedron Lett 48:7222–7224. doi:10.1016/j.tetlet.2007.07.152
MoonYH, Lee JH, Ahn JS, Nam SH, OhDK, Park DH, Chung HJ, KangS, Day DF, Kim D (2006a) Synthesis, structure analyses and char-acterization of novel epigallocatechin gallate (EGCG) glycosides
using a glucansucrase from Leuconostoc mesenteroides B-129CB.J Agric Food Chem 54:1230–1237. doi:10.1021/jf052359i
MoonYH, Lee JH, Jhon DY, JunWJ, Kang SS, Sim J, Choi H,Moon JH,Kim D (2007b) Synthesis and characterization of novel quercetin-a-D-glucopyranosides using glucansucrase from Leuconostocmesenteroides. Enzym Microb Technol 40:1124–1129. doi:10.1016/j.enzmictec.2006.08.019
Moon YM, Nam SH, Kang J, Kim YM, Lee JH, Kang HK, Breton V, JunWJ, Park KD, Kimura A, Kim D (2007a) Enzymatic synthesis andcharacterization of arbutin glucosides using glucansucrase fromLeuconostoc mesenteroides B-1299CB. Appl MicrobiolBiotechnol 77:559–567. doi:10.1007/s00253-007-1202-7
Moreno-Perez S, Filice M, Guisan JM, Fernandez-Lorente G (2013)Synthesis of ascrobyl oleate by transesterification of olive oil wihascorbic acid in polar organic media catalyzed by immobilized li-pases. Chem Phys Lipids 174:48–54. doi:10.1016/j.chemphyslip.2013.06.003
Murad S, Grove D, Lindberg KA, Reynolds G, Sivarajah A, Pinnell SR(1981) Regulation of collagen synthesis by ascorbic acid. Proc NatlAcad Sci U S A 78:2879–2882
Murase H, Moon JH, Yamauchi R, Kato K, Kunieda T, Yoshikawa T,Terao J (1998) Antioxidant activity of a novel vitamin E derivative,2-(α-L-glucopyranosyl) methyl-2, 5, 7, 8-tetramethylchroman-6-ol.Free Radic Biol Med 24:217–225. doi:10.1016/S0891-5849(97)00221-9
Nagai M, Watanabe Y, Nomura M (2009) Synthesis of acyl arbutin by animmobilized lipase and its suppressive ability against lipid oxidationin a bulk system and O/Wemulsion. Biosci Biotechnol Biochem 73:2501–2505
Nakahara K, Kontani M, Ono H, Kodama T, Tanaka T, Ooshima T,Hamada S (1995) Glycosyltransferase from Streptococcus sobrinuscatalyzes glycosylation of catechin. Appl Environ Microbiol 61:2768–2770
Nazir N, Koul S, Qurishi MA, Taneja SC, Qazi GN (2009) Lipase-catalyzed regioselective protection/deprotection of hydroxyl groupsof the isoflavone irilone isolated from Iris germanica. BiocatalBiotransfor 27:118–123. doi:10.1080/10242420802583457
Ncanana S, Burton S (2007) Oxidation of 8-hydroxyquinoline catalyzedby laccase from Trametes pubescens yields an antioxidant aromaticpolymer. J Mol Catal B Enzym 44:66–71. doi:10.1016/j.molcatb.2006.09.005
Nelson FP, Rumsfield J (1988) Cosmetics: content and function. Int JDermatol 27:665–672
Nicotra S, Cramarossa MR, Mucci A, Pagnoni UM, Riva S, Forti L(2004) Biotransformation of resveratrol: synthesis of trans-dehydrodimers catalyzed by laccases from Myceliophtorathermophyla and from Trametes pubescens. Tetrahedron 60:595–600. doi:10.1016/j.tet.2003.10.117
Nie G, Liu H, Chen Z, Wang P, Zhao G, Zheng Z (2012b) Synthesis ofpropyl gallate from tannic acid catalyzed by tannase fromAspergillus oryzae: process optimization of transesterification in an-hydrous media. J Mol Catal B Enzym 82:102–108. doi:10.1016/j.molcatb.2012.06.003
Nie G, Zheng Z, Jin W, Gong G, Wang L (2012a) Development of atannase biocatalyst based on bio-imprinting for the production ofpropyl gallate by transesterification in organic media. J Mol CatalB Enzym 78:32–37. doi:10.1016/j.molcatb.2012.01.007
Nie G, Zheng Z, Yue W, Liu Y, Liu H, Wang P, Zhao G, Cai W, Xue Z(2014) One-pot synthesis of propyl gallate by a novel whole-cellbiocatalyst. Process Biochem 49:277–282. doi:10.1016/j.procbio.2013.11.009
Nishimura T, Kometani T, Takii H, Terada Y, Okada S (1994) Acceptorspecificity in the glycosylation reaction of Bacillus subtilis X-23 α-amylase towards various phenolic compounds and the structure ofkojic acid glucoside. J Ferment Bioeng 78:37–41
Appl Microbiol Biotechnol
Nohynek GI, Antignac E, Re T, Toutain H (2010) Safety assessment ofpersonal care products/cosmetics and their ingredients. Toxicol ApplPharmacol 243:239–259. doi:10.1016/j.taap.2009.12.001
Papadopoulou AA, Katsoura MH, Chatzikonstantinou A, Kyriakou E,Polydera A, Tzakos A, Stamatis H (2013) Enzymatic hybridizationof α-lipoic acid with bioactive compounds in ionic solvents.Bioresour Technol 136:41–48. doi:10.1016/j.biortech.2013.02.067
Park DW, Kim JS, Haam S, Kim HS, Kim WS (2001) Lipase-catalysedsynthesis of β-methylglucoside esters containing an α-hydroxy ac-id. Biotechnol Lett 23:1947–1952
Park S, Viklund F, Hult K, Kazlauskas RJ (2003) Vacuum-driven lipase-catalysed direct condensation of L-ascorbic acid and fatty acids inionic liquids: synthesis of a natural surface active antioxidant. GreenChem 5:715–719. doi:10.1039/B307715B
Park TH, Choi KW, Park CS, Lee SB, Kang HY, Shon KJ, Park JS, Cha J(2005) Substrate specificity and transglycosylation catalyzed by athermostable β-glucosidase from marine hyperthermophileThermotoga neapolitana. Appl Microbiol Biotechnol 69:411–422.doi:10.1007/s00253-005-0055-1
Passicos E, Santarelli X, Coulon D (2004) Regioselective acylation offlavonoids catalyzed by immobilized Candida antarctica lipase un-der reduced pressure. Biotechnol Lett 26:1073–1076
Pedersen NR, Halling PJ, Pedersen LH, Wimmer R, Matthiesen R,Veltman OR (2002) Efficient transesterification of sucrose catalysedby the metalloprotease thermolysin in dimethylsulfoxide. FEBS Lett519:181–184. doi:10.1016/S0014-5793(02)02753-9
Pedersen NR, Wimmer R, Matthiesen R, Pedersen LH, Gessesse A(2003) Synthesis of sucrose laurate using a new alkaline protease.Tetrahedron Asymmetry 14:667–673. doi:10.1016/S0957-4166(03)00086-7
Pirozzi D, Greco G Jr (2004) Activity and stability of lipases in thesynthesis of butyl lactate. Enzym Microb Technol 34:94–100. doi:10.1016/j.enzmictec.2003.01.002
Pleiss J, FischerM, Schmid R (1998) Anatomy of lipase binding sites: thescissile fatty acid binding site. Chem Phys Lipids 93:67–80. doi:10.1016/S0009-3084(98)00030-9
Prasad D, Grupt RK, Venkataratnam GS, Kamin NR, Gowthaman MK(2011) Utilization of bahera fruits for production of tannase andgallic acid byAspergillus heteromorphusMTCC5466 and synthesisof propyl gallate thereof. Global J Biotech Biochem 6:119–128
Prodanović R, Milosavić N, Sladić D, Zlatović M, Božić B, VeličkovićTĆ, Vujčić Z (2005) Transglucosylation of hydroquinone catalysedbyα-glucosidase from baker’s yeast. J Mol Catal B Enzym 35:142–146. doi:10.1016/j.molcatb.2005.06.011
Raab T, Bel-Rhid R, Williamson G, Hansen CE, Chaillot D (2007)Enzymatic galloylation of catechins in room temperature ionic liq-uids. J Mol Catal B Enzym 44:60–65. doi:10.1016/j.molcatb.2006.09.003
Radzi SM, Rahman NJA, Noor HM, Ariffin N (2014) Enzymatic synthe-sis of olive-based ferulate esters: optimization by response surfacemethodology. IJISR 8:762–765
Raku T, Tokiwa Y (2003) Regioselective synthesis of kojic acid esters byBacillus subtilis protease. Biotechnol Lett 25:969–974. doi:10.1023/A:1024088303960
Rejasse B, Maugard T, Legoy MD (2003) Enzymatic procedures for thesynthesis of water-soluble retinol derivatives in organic media.Enzym Microb Technol 32:312–320. doi:10.1016/S0141-0229(02)00289-2
Reyes-Duarte D, Lopez-Cortes N, Torres P, Comelles F, Parra JL, Pena S,Ugidos AV, Ballesteros A, Plou FJ (2011) Synthesis and propertiesof ascorbyl esters catalyzed by lipozyme TL IM using triglyceridesas acyl donors. J Am Oil Chem Soc 88:57–64. doi:10.1007/s11746-010-1643-5
Riva S (1996) A two-step efficient chemoenzymatic synthesis of flavo-noid glycoside malonates. J Nat Prod 59:618–621. doi:10.1021/np960239m
Roenne TH, Xu X, Tan T (2005) Lipase-catalyzed esterification of lacticacid with straight-chain alcohols. JAOCS 82:881–885
Sabally K, Karboune S, St-Louis R, Kermasha S (2006) Lipase-catalyzedtransesterification of trilinolein or trilinolenin with selected phenolicacids. JAOCS 83:101–107
Salas MP, Celiz G, Geronazzo H, Daz M, Resnik SL (2011) Antifungalactivity of natural and enzymatically-modified flavonoids isolatedfrom citrus species. Food Chem 124:1411–1415. doi:10.1016/j.foodchem.2010.07.100
Salem JH, Humeau C, Chevalot I, Harscoat-Schiavo C, Vanderesse R,Blanchard F, Fick F (2010) Effect of acyl donor chain length onisoquercitrin acylation and biological activities of correspondingesters. Process Biochem 45:382–389. doi:10.1016/j.procbio.2009.10.012
Sato T, Nakagawa H, Kurosu J, Yoshida K, Tsugane T, Shimura S,Kirimura K, Kino K, Usami S (2000) Alpha-anomer-selectiveglucosylation of (+)-catechin by the crude enzyme, showingglucosyl transfer activity, of Xanthomonas campestris WU-9701. JBiosci Bioeng 90:625–630
Seo DH, Jung JH, Ha SJ, Cho HK, Jung DH, Kim TJ, Baek NI, Yoo SH,Part CS (2012b) High-yield enzymatic bioconversion of hydroqui-none to α-arbutin, a powerful skin lightening agent, byamylosucrase. Appl Microbiol Biotechnol 94:1189–1197. doi:10.1007/s00253-012-3905-7
Seo DH, Jung JH, Lee JE, Jeon EJ, Kim W, Park CS (2012a)Biotechnological production of arbutins (α- and β-arbutins), skin-lightening agents, and their derivatives. Appl Microbiol Biotechnol95:1417–1425. doi:10.1007/s00253-012-4297-4
Seo ES, Kang J, Lee JH, Kim GE, Kim GJ, Kim D (2009) Synthesis andcharacterization of hydroquinone glucoside using Leuconostocmesenteroides dextransucrase. Enzym Microb Technol 45:355–360. doi:10.1016/j.enzmictec.2009.07.011
Sharma P (2011) Cosmeceuticals: regulatory scenario in the US, Europeand India. Int J Pharm Technol 3:1512–1535
Sharma S, Gupta MN (2003) Synthesis of antioxidant propyl gallateusing tannase from Aspergillus niger van Teighem in nonaqueousmedia. Bioorg Med Chem Lett 13:395–397. doi:10.1016/S0960-894X(02)00977-0
Sharma S, Saxena RK (2012) Evaluation of the versatility of the tannasesproduced from Aspergillus niger and Penicillium variable with re-spect to gallic acid production, gallate ester synthesis, animal feedimprovement, tannery effluent degradation and tannin stain remov-al. Res Biotechnol 3:9–20
Shin MH, Cheong NY, Lee JH, Kim KH (2009) Transglucosylation ofcaffeic acid by a recombinant sucrose phosphorylase in aqueousbuffer and aqueous-supercritical CO2 media. Food Chem 115:1028–1033. doi:10.1016/j.foodchem.2009.01.013
Shogren RL, Biswas A (2013) Preparation of starch–sodium lignosulfo-nate graft copolymers via laccase catalysis and characterization ofantioxidant activity. Carbohydr Polym 91:581–585. doi:10.1016/j.carbpol.2012.08.079
Stevenson DE, Wibisono R, Jensen DJ, Stanley RA, Cooney JM (2006)Direct acylation of flavonoid glycosides with phenolic acidscatalysed by Candida antarctica lipase B (Novozym 435®).Enzym Microb Technol 39:1236–1241. doi:10.1016/j.enzmictec.2006.03.006
Sugimoto K, Nishimura T, Nomura K, Sugimoto K, Kuriki T (2003)Synthesis of arbutin α-glucosides and a comparison of their inhibi-tory effects with those ofα-arbutin and arbutin on human tyrosinase.Chem Pharm Bull 51:798–801
Sugimoto K, Nomura J, Nishimura T, Kiso T, Sugimoto K, Kuriki T(2005) Synthesis of α-arbutin-α-glycosides and their inhibitory ef-fects on human tyrosinase. J Biosci Bioeng 99:272–276
Sugimoto K, Nomura K, Nishiura H, Ohdan K, Nishimura T, Hayashi H,Kuriki T (2007) Novel transglucosylating reaction of sucrose
Appl Microbiol Biotechnol
phosphorylase to carboxylic compounds such as benzoic acid. JBiosci Bioeng 104:22–29. doi:10.1263/jbb.104.22
Sun S, Qin F, Bi Y, Chen J, Yang G, Liu W (2013b) Enhancedtransesterification of ethyl ferulate with glycerolfor preparing glyc-eryl diferulate using a lipase in ionic liquids as reaction medium.Biotechnol Lett 35:1449–1454. doi:10.1007/s10529-013-1222-6
Sun S, Shan L, Liu Y, Jin Q, Wang X, Wang Z (2007) A novel, twoconsecutive enzyme synthesis of feruloylated monoacyl- anddiacyl-glycerols in a solvent-free system. Biotechnol Lett 29:1947–1950. doi:10.1007/s10529-007-9486-3
Sun S, Shan L, Liu Y, Jin Y, Jin Q, Song Y, Wang X (2009) Solvent-freeenzymatic synthesis of feruloylated diacylglycerols and kineticstudy. J Mol Catal B Enzym 57:104–108. doi:10.1016/j.molcatb.2008.07.010
Sun S, Song F, Bi Y, Yang G, Liu W (2013a) Solvent-free enzymatictransesterification of ethyl ferulate and monostearin: optimized byresponse surface methodology. J Biotechnol 164:340–345. doi:10.1016/j.jbiotec.2013.01.013
Sun S, Zhu S, Bi Y (2014) Solvent-free enzymatic synthesis offeruloylated structured lipids by the transesterification of ethylferulate with castor oil. Food Chemistry 158:292–295. doi:10.1016/j.foodchem.2014.02.146
Takami M, Hidaka N, Miki S, Suzuki Y (1994) Enzymatic synthesis ofnovel phosphatidylkojic acid and phosphatidylarbutin, and their in-hibitory effects on tyrosinase activity. Biosci Biotechnol Biochem58:1716–1717. doi:10.1271/bbb.58.1716
Tan Z, Shahidi F (2011) Chemoenzymatic synthesis of phytosterylferulates and evaluation of their antioxidant activity. J Agric FoodChem 59:12375–12383. doi:10.1021/jf2034237
Tan Z, Shahidi F (2012) A novel chemoenzymatic synthesis ofphytosteryl caffeates and assessment of their antioxidant activity.Food Chem 133:1427–1434. doi:10.1016/j.foodchem.2012.02.030
Tan Z, Shahidi F (2013) Phytosteryl sinapates and vanillates:chemoenzymatic synthesis and antioxidant capacity assessment.Food Chem 138:1438–1447. doi:10.1016/j.foodchem.2012.10.093
Theodosiou E, Katsoura MH, Loutrari H, Purchartova K, Kren V, KolisisFN, Stamatis H (2009) Enzymatic preparation of acylated deriva-tives of silybin in organic and ionic liquid media and evaluation oftheir antitumour proliferative activity. Biocatal Biotransfor 27:161–169. doi:10.1080/10242420902937777
Tokiwa Y, Kitagawa M, Raku T (2007a) Enzymatic synthesis of arbutinundecylenic acid ester and its inhibitory effect on mushroom tyrosi-nase. Biotechnol Lett 29:481–486. doi:10.1007/s10529-006-9267-4
Tokiwa Y, Kitagawa M, Raku T, Yanagitani S, Yoshino K (2007b)Enzymatic synthesis of arbutin undecylenic acid ester and its inhib-itory effect on melanin synthesis. Bioorg Med Chem Lett 17:3105–3108. doi:10.1016/j.bmcl.2007.03.039
Topakas E, Stamatis H, Biely P, Kekos D, Macris BJ, Christakopoulos P(2003b) Purification and characterization of a feruloyl esterase fromFusarium oxysporum catalyzing esterification of phenolic acids internary water-organic solvent mixtures. J Biotechnol 102:33–44.doi:10.1016/S0168-1656(02)00363-2
Topakas E, Stamatis H, Biely P, Christakopoulos P (2004) Purificationand characterization of a type B feruloyl esterase (StFae-A) from thethermophilic fungus Sporotrichum thermophile. Appl MicrobiolBiotechnol 63:686–690
Topakas E, Stamatis H, Mastihubova M, Biely P, Kekos D, Macris BJ,Christakopoulos P (2003a) Purification and characterization of aFusarium oxysporum feruloyl esterase (FoFAE-I) catalysingtransesterification of phenolic acid esters. Enzym Microb Technol33:729–737. doi:10.1016/S0141-0229(03)00213-8
Torres C, Otero C (1999) Part I: enzymatic synthesis of lactate andglycolate esters of fatty alcohols. Enzym Microb Technol 25:745–752. doi:10.1016/S0141-0229(99)00117-9
Torres C, Otero C (2001) Part III: direct enzymatic esterification of lacticacid with fatty acids. EnzymMicrob Technol 29:3–12. doi:10.1016/S0141-0229(01)00344-1
Torres P, Kunamneni A, Ballesteros A, Plou FJ (2008a) Enzymatic mod-ification of ascorbic acid and alpha-tocopherol to enhance their sta-bility in food and nutritional applications. Open Food Sci J 2:1–9
Torres P, Reyes-Duarte D, Lopez-Cortes N, Ferrer M, Ballesteros A, PlouFJ (2008b) Acetylation of vitamin E byCandida antarctica lipase Bimmobilized on different carries. Process Biochem 43:145–153. doi:10.1016/j.procbio.2007.11.008
Toth G, Hensler D (1952) The enzymatic synthesis of gallic acid deriva-tives. Acta Chim II 10:209–212
Tsuchiyama M, Sakamoto T, Fujita T, Murata S, Kawasaki H (2006)Esterification of ferulic acid with polyols using a ferulic acid esterasefrom Aspergillus niger. Biochim Biophys Acta 7:1071–1079. doi:10.1016/j.bbagen.2006.03.022
Tsuchiyama M, Sakamoto T, Tanimori S, Murata S, Kawasaki H (2007)Enzymatic synthesis of hydroxycinnamic acid glycerol esters usingtype A feruloyl esterase from Aspergillus niger. Biosci BiotechnolBiochem 71:2606–2609
Tung RC, BergfeldWF, Vidimos AT, Remzi BK (2000)α-Hydroxy acid-based cosmetic procedures. Am J Chin Dermatol 1:81–88
Uzan E, Portet B, Lubrano C, Milesi S, Favel A, Lesage-Meessen L,Lomascolo A (2011) Pycnoporus laccase-mediated bioconversionof rutin to oligomers suitable for biotechnology applications. ApplMicrobiol Biotechnol 90:97–105. doi:10.1007/s00253-010-3075-4
Vafiadi C, Topakas E, Alderwick LJ, Besra GS, Christakopoulos P(2007a) Chemoenzymatic synthesis of feruloyl-D-arabinose as apotential anti-mycobacterial agent. Biotechnol Lett 29:1771–1774
Vafiadi C, Topakas E, Alissandratos A, Faulds CB, Christakopoulos P(2008b) Enzymatic synthesis of butyl hydroxycinnamates and theirinhibitory effect on LDL-oxidation. J Biotechnol 133:497–504
Vafiadi C, Topakas E, Bakx EJ, Schols HA, Christakopoulos P (2007b)Structural characterization of ESI-MS of feruloylated arabino-oligosaccharides synthesized by chemoenzymatic esterification.Molecules 12:1367–1375
Vafiadi C, Topakas E, Christakopoulos P (2008a) Preparation of multi-purpose cross-linked enzyme aggregates and their application toproduction of alkyl ferulates. J Mol Catal B Enzym 54:35–41. doi:10.1016/j.molcatb.2007.12.005
Vafiadi C, Topakas E, Christakopoulos P, Faulds CB (2006) The feruloylesterase system of Talaromyces stipitatus: determining the hydrolyt-ic and synthetic specificity of TsFaeC. J Biotechnol 125:210–221
Vafiadi C, Topakas E, Wong KKY, Suckling ID, Christakopoulos P(2005) Mapping the hydrolytic and synthetic selectivity of a typeC feruloyl esterase (StFaeC) from Sporotrichum thermophile usingalkyl ferulates. Tetrahedron Asymmetry 16:373–379. doi:10.1016/j.tetasy.2004.11.037
Vafiadi C, Topakas E, Nahmias VR, Faulds CB, Christakopoulos P(2009) Feruloyl esterase-catalyzed synthesis of glycerol sinapateusing ionic liquid mixtures. J Biotechnol 139:124–129. doi:10.1016/j.jbiotec.2008.08.008
Vavrikova E, Vacek J, Valentova K, Marchol P, Ulrichova J, Kuzma M,Kren V (2014) Chemo-enzymatic synthesis of silybin and 2,3-dehydrosilybin dimers. Molecules 19:4115–4134. doi:10.3390/molecules19044115
Viklund F, Alander J, Hult K (2003) Antioxidative properties and enzy-matic synthesis of ascorbyl FA esters. JAOCS 80:795–799
Viskupicova J, Danihelova M, Ondrejovic M, Liptaj T, Sturdik E (2010)Lipophilic rutin derivatives for antioxidant protection of oil-basedfoods. Food Chem 123:45–50. doi:10.1016/j.foodchem.2010.03.125
Wang J, Gu SS, Cui HS,Wu XY,Wu FA (2014) A novel continuous flowbiosynthesis of caffeic acid phenethyl ester from alkyl caffeate andphenethanol in a packed bed microreactor. Bioresour Technol 158:39–47. doi:10.1016/j.biortech.2014.01.145
Appl Microbiol Biotechnol
Wang J, Gu SS, Cui HS, Yang LQ, Wu XY (2013) Rapid synthesis ofpropyl caffeate in ionic liquid using a packed bed enzymemicroreactor under continuous-flow conditions. Bioresour Technol149:367–374. doi:10.1016/j.biortech.2013.09.098
Wang J, Wang S, Li Z, Gu S, Wu X, Wu F (2015) Ultrasound irradiationaccelerates the lipase-catalyzed synthesis of methyl caffeate in anionic liquid. J Mol Catal B Enzym 111:21–28. doi:10.1016/j.molcatb.2014.11.006
Watanabe Y, Kuwabara K, Adachi S, Nakanishi K, Matsuno R (2003)Production of saturated acyl-L-ascorbate by immobilized lipaseusing a continuous stirred tank reactor. J Agric Food Chem 51:4628–4632
WatanabeY, NagaiM, YamanakaK, Jose K, NomuraM (2009) Synthesisof lauroyl phenolic glycoside by immobilized lipase in organic sol-vent and its antioxidative activity. J Biochem Eng 43:261–265. doi:10.1016/j.bej.2008.10.008
Watanabe Y, Sawahara Y, Nosaka H, Yamanaka K, Adachi S (2008)Enzymatic synthesis of conjugated linoleoyl ascorbate in acetone.Biochem Eng J 40:268–372. doi:10.1016/j.bej.2008.01.007
Weetall HH (1985) Enzymatic synthesis of gallic acid esters. ApplBiochem Biotechnol 11
Wei D, Gu C, Song Q, Su W (2003) Enzymatic esterification for glyco-side lactate synthesis in organic solvent. EnzymMicrob Technol 33:508–512. doi:10.1016/S0141-0229(03)00156-X
Wei DZ, Zou P, Tu MB, Zheng H (2002) Enzymatic synthesis of ethylglucoside lactate in non-aqueous system. J Mol Catal B Enzym 18:273–278. doi:10.1016/S1381-1177(02)00106-6
Widjaja A, Yeh TH, Ju YH (2008) Enzymatic synthesis of caffeic acidphenethyl ester. J Chin Inst Chem Eng 39:413–418. doi:10.1016/j.jcice.2008.05.003
Woo HJ, Kang HK, Nguyen TTH, Kim GE, Kim YM, Park JS, Kim D,Cha J, Moon YH, Nam SH, Xia YM, Kimura A, Kim D (2012)Synthesis and characterization of ampelopsin glucosides usingdextransucrase from Leuconostoc mesenteroides B-1299CB4:glucosylation enhancing physicochemical properties. EnzymMicrob Technol 51:311–318. doi:10.1016/j.enzmictec.2012.07.014
Xiao Y, Yang L, Mao P, Zhao Z, Lin X (2011) Ultrasound-promoted enzy-matic synthesis of troxerutin esters in nonaqueous solvents. UltrasonSonochem 18:303–309. doi:10.1016/j.ultsonch.2010.06.010
Xiao YM, Wu Q, Wu WB, Zhang QY, Lin XF (2005) Controllable re-gioselective acylation of rutin catalyzed by enzymes in non-aqueoussolvents. Biotechnol Lett 27:1591–1595. doi:10.1007/s10529-005-2513-3
Xin JY, Chen LI, Zhang YX,Wen RR, Zhao DM, Xia CG (2011) Lipase-catalyzed synthesis of a-tocopheryl ferulate. Food Biotechnol 25:43–57. doi:10.1080/08905436.2011.547116
Xin JY, Zhang L, Chem LL, Zheng Y, Wu XM, Xia CG (2009) Lipase-catalyzed synthesis of feruloyl oleins in solvent-free medium. FoodChem 112:640–645. doi:10.1016/j.foodchem.2008.06.024
Yan H, Wang Z, Chen L (2009) Kinetic resolution of α-lipoic acid viaenzymatic differentiation of a remote stereocenter. J Ind MicrobiolBiotechnol 36:643–648. doi:10.1007/s10295-009-0531-1
Yang H, Mu Y, Chen H, Xiu Z, Yang T (2013) Enzymatic synthesis offeruloylated lysophospholipid in a selected organic solvent medium.Food Chem 141:3317–3322. doi:10.1016/j.foodchem.2013.06.012
Yang HD,Wang Z, Chen LJ (2009) Kinetic resolution of a-lipoic acid viaenzymatic differentiation of a remote sterocenter. J Ind MicrobiolBiotechnol 36:643–648. doi:10.1007/s10295-009-0531-1
Yang RL, Li N, Li RF, Smith TJ, Zong MH (2010a) A highly regioselec-tive route to arbutin esters by immobilized lipase from Penicillium
expansum. Bioresour Technol 101:1–5. doi:10.1016/j.biortech.2009.07.067
Yang RL, Li N, Ye M, Zong MH (2010b) Highly regioselective synthesisof novel aromatic esters of arbutin catalyzed by immobilized lipasefrom Penicillium expansum. J Mol Catal B Enzym 67:41–44. doi:10.1016/j.molcatb.2010.07.003
Yang Z, Glasius M, Xu X (2012) Enzymatic transesterification of ethylferulate with fish oil and reaction optimization by response surfacemethodology. Food Technol Biotechnol 50:88–97
Yin C, Liu T, Tan T (2006) Synthesis of vitamin A esters by immobilizedCandida sp. lipase in organic media. Chin J Chem Eng 14:81–86.doi:10.1016/S1004-9541(06)60041-4
Yin C, Zhang C, GaoM (2011) Enzyme-catalyzed synthesis of vitamin Esuccinate using a chemically modified Novozym-435. Chin J ChemEng 19:135–139. doi:10.1016/S1004-9541(09)60189-0
Yu XW, Li YQ (2005) Microencapsulated mycelium-bound tannase fromAspergillus niger an efficient catalyst for esterification of propylgallate in organic solvents. Appl Biochem Biotechnol 126:177–187
YuXW, Li YQ (2008) Expression of Aspergillus oryzae tannase inPichiapastoris and its application in the synthesis of propyl gallate inorganic solvent. Food Technol Biotechnol 46:80–85
Yu XW, Li YQ, Zhou SH, Zheng YY (2007) Synthesis of propyl gallateby mycelium-bound tannase from Aspergillus niger in organic sol-vent. World J Microbiol Biotechnol 23:1091–1098. doi:10.1007/s11274-006-9338-7
Yu Y, Zheng Y, Quan J, Wu CY, Wang YJ, Brandford-White C, Zhu LM(2010) Enzymatic synthesis of feruloylated lipids: comparison of theefficiency of vinyl ferulate and ethyl ferulate as substrates. J Am OilChem Soc J 87:1443–1449. doi:10.1007/s11746-010-1636-4
Zeuner B, Ståhlberg T, van BuuON,Kunov-Kruse AJ, RiisagerA,MeyerAS (2011) Dependency of the hydrogen bonding capacity of thesolvent anion on the thermal stability of feruloyl esterases in ionicliquid systems. Green Chem 13:1550–1557. doi:10.1039/C1GC15115K
Zhang DH, Li YQ, Li C, Lv YQ, Yv-Qin L, Yang L (2012) Kinetics ofenzymatic synthesis of L-ascorbyl acetate by lipozyme TLIM andNovozym 435. Biotechnol Bioprocess Eng 17:60–66. doi:10.1007/s12257-011-0249-6
Zhang S (2015) Novel trends for use of microbial tannases. Prep BiochemBiotechnol 45:221–232. doi:10.1080/10826068.2014.907182
Zhao H, Liu J, Lv F, Ye R, Bie X, Zhang C, Lu Z (2014) Enzymaticsynthesis of lard-based ascorbyl esters in a packed-bed reactor: op-timization by response surface methodology and evaluation of anti-oxidant properties. LWT Food Sci Technol 57:393–399. doi:10.1016/j.lwt.2013.12.015
Zheng MM, Wang L, Huang FH, Guo PM, Wei F, Deng QC, Zheng C,Wan CY (2013) Ultrasound irradiation promoted lipase-catalyzedsynthesis of flavonoid esters with unsaturated fatty acids. J MolCatal B Enzym 95:82–88. doi:10.1016/j.molcatb.2013.05.028
Zheng Y, Quan J, Zhu LM, Jiang B, Nie HL (2008) Optimization ofselective lipase-catalyzed feruloylated monoacylglycerols by re-sponse surface methodology. J Am Oil Chem Soc 85:635–639.doi:10.1007/s11746-008-1248-4
Zhu S, Li Y, Li Z, Ma C, Lou Z, Yokoyama W, Wang H (2014) Lipase-catalyzed synthesis of acetylated EGCG and antioxidant propertiesof the acetylated derivatives. Food Res Int 56:279–286. doi:10.1016/j.foodres.2013.10.026
Ziaullah HPVR (2013) An efficient microwave-assisted enzyme-cata-lyzed regioselective synthesis of long chain acylated derivatives offlavonoid glycosides. Tetrahedron Lett 54:1933–1937. doi:10.1016/j.tetlet.2013.01.103
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